Search

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis and a more effective immune response than patients with microsatellite stable (MSS) CRC. Moreover, activated platelets play a crucial role in modulating innate immune cells. Mean platelet volume (MPV) is an indicator of platelet activation. This study is to examine the association between MPV and MSI status in CRC. METHODS: We collected the clinical and pathological variables of 424 CRC patients diagnosed at the Harbin Medical University Cancer Hospital from January 2018 to December 2018. Associations between MPV levels and MSI status were examined. Propensity score matching (PSM) was performed to reduce the possibility of selection bias. RESULTS: 424 CRC patients were divided into low-MPV group and high-MPV group according to the optimal cut-off value of MPV. 131 high-MPV patients were matched to low-MPV counterparts in a 1:1 ratio by propensity score matching. As MPV levels increased, the percentage of patients with MSI-H reduced. Furthermore, compared with MSS group, the MSI-H group had a significantly lower MPV levels (p= 0.003 after matching). In addition, logistic regression analysis identified reduced MPV as an independent risk factor for MSI-H in CRC patients after controlling for other potential parameters. CONCLUSION: Lower MPV is associated with MSI-H subtype of CRC. Further study on MPV in MSI-H CRC is warranted.

BACKGROUND Ovarian cancer (OC) is one of the most malignant gynecological cancers. Platelets play a profound role in cancer growth and metastasis. Platelet distribution width (PDW) is an indicator of platelet activation and is altered in malignancies. However, the prognostic value of PDW in OC remains unclear. This present study aimed to investigate the predictive significance of PDW in OC. METHODS 221 OC patients, between January 2013 and December 2013, were included in this study. The correlations between PDW and clinicopathological features were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. RESULTS Of the 221 patients, increased PDW levels were observed in 163 (73.6%) patients. Kaplan-Meier analysis revealed that higher PDW levels were associated with poor progression-free survival and overall survival (both p< 0.001). Cox-regression analysis confirmed the independent predictive value of PDW on overall survival (HR = 2.820, 95% CI = 1.776-4.476, p< 0.001). CONCLUSION Higher PDW levels predict poor prognosis in patients with OC. Elevated PDW may be a novel target for therapy.

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

// Xin Wang 1, * , Ming-Ming Cui 1, * , Yangyang Xu 2, 3, * , Li Liu 3 , Ye Niu 4 , Tiemin Liu 1, 5 , Zhi-Ping Liu 6 , Rui-Tao Wang 1, 3 and Kai-Jiang Yu 7, 3 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China 2 Department of Urinary Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China 3 Heilongjiang Academy of Medical Science, Harbin, Heilongjiang 150081, China 4 Department of Geriatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China 5 Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA 6 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 7 Department of Intensive Care Unit, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China * These authors have contributed equally to this work Correspondence to: Rui-Tao Wang, email: ruitaowang@126.com Kai-Jiang Yu, email: kaijiang_yu@yeah.net Keywords: bladder cancer, mean platelet volume, prognosis Received: February 13, 2017 Accepted: June 10, 2017 Published: July 12, 2017 ABSTRACT Background: Altered mean platelet volume (MPV) is implicated in a wide range of cancers. However, the prognostic role of MPV in muscle-invasive bladder cancer (MIBC) remains largely unknown. The purpose of this study was to elucidate the predictive significance of MPV in MIBC. Method: The retrospective study included 218 consecutive MIBC 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. Result: Of the 218 patients, low MPV levels were detected in 141 (64.7 %) patients. Reduced MPV was associated with T stage and histology grade (p < 0.05). In the Kaplan-Meier analysis, decreased MPV was significantly associated with a poorer overall survival (p = 0.007). In the multivariate Cox model, decreased MPV was an independent prognostic index for overall survival (HR=2.023, 95% CI=1.050-3.897, p = 0.025). Conclusion: MPV is easily available in routine blood test. Our results demonstrated that reduced MPV could be regarded as a potential prognosis indicator for clinical outcome in MIBC.

// Huan Zhang 1, * , Li Liu 2, * , Shuang Fu 1, * , Yan-Song Liu 3 , Changsong Wang 3 , Tiemin Liu 1, 4 , Zhi-Ping Liu 5 , Rui-Tao Wang 1, 6 and Kai-Jiang Yu 3, 6 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 2 Department of Histology and Embryology, Harbin Medical University, Harbin, Heilongjiang, 150081, China 3 Department of Intensive Care Unit, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 4 Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA 5 Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA 6 Heilongjiang Academy of Medical Science, Harbin, Heilongjiang, 150081, China * These authors have contributed equally to this work Correspondence to: Rui-Tao Wang, email: ruitaowang@126.com Kai-Jiang Yu, email: kaijiang_yu@yeah.net Keywords: laryngeal cancer, platelet distribution width, prognosis, survival Received: March 29, 2017 Accepted: May 01, 2017 Published: May 30, 2017 ABSTRACT Background: Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet indices in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet indices in laryngeal cancer. Results: Of the 241 patients, high platelet distribution width (PDW) levels were observed in 116 (48.1 %) patients. In the Kaplan-Meier analysis, increased PDW was significantly associated with a poorer overall survival (p < 0.001). In the multivariate Cox model, PDW was an independent prognostic index for overall survival (HR=4.381, 95% CI=2.313-8.298, P < 0.001). Method: The retrospective study included 241 consecutive patients with laryngeal cancer between January 2009 and December 2009. The relationships between PDW and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. Conclusions: Elevated PDW might be a novel prognostic marker in laryngeal cancer.

// Xin Zhang 1, * , Ming-Ming Cui 1, * , Shuang Fu 1 , Lu-Lu Li 2 , Yan-Song Liu 3 , Zhi-Ping Liu 4 , Tiemin Liu 5 , Rui-Tao Wang 1 , Kai-Jiang Yu 3 1 Department of Internal Medicine, The Third Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 2 Department of Geriatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150086, China 3 Department of Intensive Care Unit, The Third Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150081, China 4 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA 5 Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, 75390, USA * These authors have contributed equally to this work Correspondence to: Rui-Tao Wang, email: ruitaowang@126.com Kai-Jiang Yu, email: kaijiang_yu@yeah.net Keywords: gastric cancer, platelet distribution width, prognosis, survival Received: September 27, 2016 Accepted: January 17, 2017 Published: February 21, 2017 ABSTRACT Background: Activated platelets promote tumor cell growth, aberrant angiogenesis, and invasion. However, the value of platelet indices for predicting survival in gastric cancer remains unknown. The goal of this study was to investigate the predictive significance of platelet indices in gastric cancer. Result: Reduced platelet distribution width (PDW) was significantly correlated with age, carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases stage. Moreover, decreased PDW correlated with a shorter overall survival in gastric cancer. Multivariate analysis identified PDW as an independent prognostic factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319-0.761, p = 0.001). Method: A total of 294 patients with gastric cancer were retrospectively analyzed between January 2009 and December 2009. The association between platelet indices and overall survival were evaluated. The prognostic analysis was carried out with Cox regression model. Conclusion: PDW is easily available with routine blood counts. Our data revealed that reduced PDW is unfavorable prognostic factor in gastric cancer. Further studies are warranted.

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 Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and second most common cause of tumor-related deaths worldwide. Activated platelets play a prominent role in tumor. Platelet distribution width (PDW) indicates platelets activation and is altered in malignancies. The aim of this study was to explore the prognostic value of PDW for overall survival (OS) in HCC patients. Methods We retrospectively reviewed 273 HCC patients at a single institution from 2010 to 2014. The relationship between PDW and clinicopathological characteristics was analyzed. Kaplan-Meier curves and multivariate Cox regression analyses were used to evaluate the relationship of PDW with OS. Results Low PDW levels were observed in 127 (46.5%) out of 273 patients. A significant correlation was found between PDW and liver cirrhosis. Median follow-up was 36 months, survival curves revealed that the patients with increased PDW had significantly shorter survival time than those with normal PDW (p= 0.001). Cox regression analysis demonstrated that PDW was an independent prognostic factor for overall survival (hazard ratio, 2.464; 95% confidence interval [CI], 1.402-4.330, p= 0.001). Conclusion PDW is significantly associated with OS in HCC. This result suggests activated platelet may affect clinical outcome and warrant continued investigation.

Background Platelets play a crucial role in breast cancer (BC) progression and metastases. Mean platelet volume (MPV) is an indicator of platelet activation. The aim of the present study was to assess whether there is a difference in MPV between patients with metastatic BC with liver metastases and those with BC without liver metastases. Methods Between January 2014 and December 2017, 211 metastatic BC patients with synchronous liver metastases and 215 BC patients without metastases were retrospectively analyzed. Patients' clinicopathological characteristics data were collected. Results MPV levels were reduced in patients with liver metastases compared with those in patients without liver metastases. There were significant differences in MPV levels according to liver metastases status both in premenopausal and in postmenopausal non-TNBC or non-HER2+ patients. Moreover, in postmenopausal HER2+ or TNBC patients, MPV levels were lower in patients with liver metastases compared with those in patients without liver metastases. In the group with non-liver metastasis, platelet distribution width was significantly associated with tumor N stage. In addition, the prevalence of BC liver metastases decreased as MPV quartiles increased. After adjusting for other risk factors, the odds ratios for liver metastases according to MPV quartiles were 1.000, 0.267 (0.134-0.530), 0.072 (0.034-0.152), and 0.137 (0.066-0.281), respectively. Conclusion MPV is reduced in BC patients with liver metastases compared with that in BC patients without metastases. Moreover, MPV is independently associated with the presence of liver metastases.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer (BC). Furthermore, growing evidence suggests that activated platelets play a crucial role in tumor and T2DM. Mean platelet volume (MPV) is a platelet index and is altered in patients with malignancies. The aim of this study was to determine whether preoperative MPV could predict survival in BC patients with T2DM. The clinical data of 266 female BC patients with T2DM and 264 female BC patients without T2DM between January 2011 and December 2011 in our center were retrospectively analyzed. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. The patients with T2DM had higher MPV levels than the patients without T2DM. Furthermore, MPV was found to be significantly associated with differentiation T2DM from non-T2DM. In addition, survival analysis revealed that the disease-specific survival and overall survival of patients with MPV ≤ 8.0 fL were significantly shorter than that of those with MPV > 8.0 fL in diabetic patients. Multivariate analysis identified MPV as an independent poor prognostic factor for survival only in patients with T2DM not in patients without T2DM. Our study first established a connection between MPV and BC patients with T2DM, suggesting that MPV was an independent prognostic factor and could be the biomarker for prognosis.

Background Platelets play a crucial role in cancer progression and metastasis. The aim of the present study was to assess the relationship between platelet indices and non-small cell lung cancer (NSCLC) with brain metastases. Methods Between January 2015 and December 2017, 232 NSCLC patients with brain metastases and 244 NSCLC patients without metastases were retrospectively analyzed. Patients' clinicopathological characteristics data were collected. Results Platelet count was increased and mean platelet volume (MPV) was reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. In addition, the prevalence of NSCLC decreased as MPV quartiles increased. After adjusting for other risk factors, the ORs (95% CIs) for NSCLC brain metastases according to MPV quartiles were 1.757 (1.024-3.015), 2.097 (1.209-3.635), 1.517 (0.874-2.635), and 1.000, respectively. Conclusions MPV is reduced in NSCLC patients with brain metastases compared with NSCLC patients without metastases. Moreover, MPV is found to be independently associated with the presence of NSCLC brain metastases.

Background: Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Platelet distribution width (PDW), a platelet index, indicates variation in platelet size. We aimed to investigate whether the combination of D-dimer and PDW could have a better performance in predicting DVT in patients with cervical carcinoma. Materials and Methods: In 198 consecutive cervical carcinoma patients without preoperative DVT, preoperative D-dimer and PDW levels were measured. Compression ultrasonography was performed in all cervical carcinoma patients before surgery, as well as one month, three months, six months, and 12 months. Results: During a median period of 12 months, 17 of the 198 patients (8.6 %) developed DVT. PDW levels were reduced and D-dimer levels were increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealed that both PDW and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.628 (95% CI: 0.556 to 0.695, p=0.142) when D-dimer was used alone, whereas it increased to 0.777 (95% CI: 0.712 to 0.833, p

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.

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.

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.

BackgroundSepsis claims over 215,000 lives and costs $16.7 billion per year in America alone. Recent studies revealed that HDL receptor scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. Using Scarb1I179N mice, a mutant SR-BI mouse model with 90% depletion in hepatic SR-BI, we previously reported that the mutant mice are susceptible to cecal ligation and puncture (CLP)-induced sepsis. However, using a hypo-AlbCreSR-BIfl/fl mouse model, Hubys group showed that the liver-specific SR-BI KO mice are not more susceptible to CLP-induced sepsis. In this study, we generated a new floxed SR-BI mouse model to clarify the contribution of hepatic SR-BI in sepsis. SR-BI is known as a receptor that plays a key role in reverse cholesterol transport (RCT) by uptaking cholesterol to the liver. So, our established AlbCreSR-BIfl/fl mice (liver-specific SR-BI KO) is an RCT deficiency mice model that can be used to understand the mechanisms of RCT protecting against sepsis and may provide new insight into the pathogenesis of sepsis. Methods and ResultsWe generated SR-BIfl/fl mice by flanking exon 2. We bred the floxed mice with AlbCre mice to generate AlbCreSR-BIfl/fl mice (liver-specific SR-BI KO mice), then the mice were backcrossed to C57BL/6J for 10 generations. As shown in Fig 1, the liver SR-BI expression was normal in SR-BIfl/fl mice as compared to C57BL/6J (B6) mice, but completely depleted in AlbCreSR-BIfl/fl mice. Using this liver-specific SR-BI KO model, we observed that a deficiency in RCT rendered the mice highly susceptible to CLP-induced sepsis as shown by 80% and 14.3% survival of SR-BIfl/fl and AlbCreSR-BIfl/fl mice, respectively. We found aggravated inflammatory cytokine production, altered leukocyte recruitment and slightly increased in the blood and peritoneal bacteria. Moreover, we found RCT deficiency mice increased both free and total cholesterol levels in serum and showed severer hemolysis in AlbCreSR-BIfl/fl mice than SR-BIfl/fl mice during CLP-induced sepsis. Importantly, when we fed AlbCreSR-BIfl/fl mice with probucol to decrease the cholesterol level in serum before performing CLP, the survival rate of AlbCreSR-BIfl/fl mice improved to 88.9%. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/051250v1_fig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@bb1fe0org.highwire.dtl.DTLVardef@129d488org.highwire.dtl.DTLVardef@14043e2org.highwire.dtl.DTLVardef@28b554_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig. 1.C_FLOATNO Mice deficient in hepatic SR-BI are susceptible to CLP-induced septic death. A, PCR genotyping of AlbCreSR-BIfl/fl mice using tail DNA. B, Western blot analysis of SR-BI expression in the liver; C, survival analysis. AlbCreSR-BIfl/fl (n = 14) and SR-BIfl/fl mice (n = 10) were treated with CLP (23G needle, half ligation) and survival was observed for 7 days. The data were expressed as the percentage of mice surviving at indicated times, and survival was analyzed by Log-Rank x2 test. D, AlbCreSR-BIfl/fl and SR-BIfl/fl mice were treated with CLP for the indicated times, and kidney injury was assessed by measuring blood urea nitrogen (BUN) levels; and E, liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels. n = 6 - 7 each group, mean {+/-} SEM. C_FIG ConclusionsDeficiency RCT resulting in abnormal metabolism of cholesterol and lipid metabolism is a risk factor in sepsis and maintain normal metabolism of cholesterol may provide a new insight for sepsis therapies.

BACKGROUND Deep venous thrombosis (DVT) is associated with severe morbidity and mortality in cancer. Mean platelet volume (MPV) is an indicator of activated platelets. OBJECTIVE We aimed to investigate whether the combination of D-dimer and MPV could have a better performance in predicting deep venous thrombosis (DVT) in patients with breast cancer. MEHTODS In 342 consecutive breast cancer patients without preoperative DVT, we measured the preoperative D-dimer and MPV levels. Compression ultrasonography was performed in all breast cancer patients before surgery, as well as one month, three months, six months, and twelve months. RESULTS During a median period of twelve months, 15 of the 234 patients (6.4%) developed DVT. MPV was reduced and D-dimer was increased in patients with DVT events compared to those without DVT. Multivariate Cox analysis revealed that both MPV and D-dimer were independent predictors for DVT events. The area under the ROC curve was 0.619 (95% CI: 0.553 to 0.681) when D-dimer was used alone, whereas it increased to 0.790 (95% CI 0.732 to 0.840, p< 0.001) with the addition of MPV. CONCLUSIONS The combination of preoperative D-Dimer and MPV improves the predictive power of postoperative DVT risk in breast cancer patients.

Background Laryngeal cancer is one of the most common malignancies in the head and neck. Activated platelets play a critical role in cancer development and progression. Altered mean platelet volume (MPV) and platelet distribution width (PDW) have been found in various types of cancer. The purpose of the current study was to investigate the association of platelet indices with laryngeal cancer. Study design The study included 216 patients with laryngeal cancer, 189 subjects with benign laryngeal disease, and 213 control subjects between January 2015 and December 2015. All participants' clinical and laboratory characteristics at initial diagnosis were collected. Result MPV was significantly lower and PDW was markedly higher in laryngeal cancer patients compared with control subjects and patients with benign laryngeal disease. A significant correlation between MPV and lymph node metastasis was found. The prevalence of laryngeal cancer increased as MPV quartiles decreased and PDW quartiles increased. Furthermore, MPV and PDW were independent risk factors for distinguishing laryngeal cancer from benign laryngeal disease. Conclusions The patients with laryngeal cancer have reduced MPV and increased PDW compared to the subjects without laryngeal cancer. In addition, MPV and PDW play different roles in laryngeal cancer from benign laryngeal disease.

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 P P

We investigated the neuroprotective effects of baicalin and the role of gut microbiota in a mouse model of cerebral ischemia-reperfusion injury. Repeated cerebral ischemia-reperfusion significantly increased plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and clusterin (a neuroinflammation biomarker). These changes correlated with cognitive decline; short-term memory deficits; abnormal long term potentiation (LTP); decreased functional connectivity (FC) between various brain regions; reduced plasticity and dendritic spine density in the hippocampus; increased levels of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα; and altered the gut microbial composition. Treatment with 50-100 mg/Kg baicalin for 7 days after cerebral ischemia-reperfusion significantly restored normal plasma levels of TMA, TMAO, and clusterin. Baicalin treatment also suppressed neuroinflammation, remodeled the gut microbial composition back to normal, and improved cognition, memory, LTP, cerebral FC, and hippocampal neuronal plasticity. The neuroprotective effects of baicalin were diminished when mice undergoing repeated cerebral ischemia-reperfusion were pretreated with broad-spectrum antibiotics to deplete gut microbial populations. This suggests the neuroprotective effects of baicalin in cerebral ischemia-reperfusion injury are mediated by the gut microbiota. It thus appears that baicalin ameliorates neuropathology in a repeated cerebral ischemia-reperfusion model mice by remodeling the gut microbiota.

Purpose. Mean platelet volume (MPV) and platelet distribution width (PDW) have been used to reflect the platelet activity in clinics. We assessed initial serum MPV and PDW levels in colorectal cancer (CRC) patients, in predicting the development of sepsis in CRC patients postoperatively. Patients and Methods. This study included 220 patients diagnosed with CRC. 55 patients were stratified to one group that developed sepsis postoperatively, and 165 patients were stratified to the other group that did not develop sepsis postoperatively. Clinical and laboratory characteristics were collected 3 days before the operation. Results. MPV (p<0.001) was significantly higher and PDW (p<0.001) was significantly lower in the sepsis group than in the nonsepsis group. Either MPV or PDW is independently associated with ICU mortality in sepsis patients with CRC. MPV is independently associated with 14-day, 28-day, and 90-day mortality and PDW is independently associated with 90-day mortality in patients with CRC. The prevalence of sepsis increased as MPV tertiles increased (p<0.001), and the prevalence of sepsis increased as PDW tertiles decreased (p<0.001). Conclusions. Serum MPV and PDW levels between CRC patients with/without sepsis postoperatively are significantly different. The initial serum MPV or PDW levels can potentially serve as a predictor of sepsis in CRC patients postoperatively.

// Shuang Fu 1, * , Zhi-Yuan Yun 1, * , Ming-Ming Cui 1 , Hongxue Meng 2 , Cheng Qian 3 , Tiemin Liu 1, 4 , Zhi-Ping Liu 5 , Rui-Tao Wang 1 and Kai-Jiang Yu 6 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China 2 Department of Pathology, Harbin Medical University Cancer Hospital, Harbin 150081, China 3 Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, China 4 Division of Hypothalamic Research, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA 5 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 6 Department of Intensive Care Unit, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China * These authors have contributed equally to this work Correspondence to: Rui-Tao Wang, email: ruitaowang@126.com Kai-Jiang Yu, email: kaijiang_yu@yeah.net Keywords: breast cancer, carcinoembryonic antigen, cancer antigen 15-3, platelet distribution width, fibrinogen Received: December 20, 2016 Accepted: June 02, 2017 Published: June 29, 2017 ABSTRACT Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females. However, mammographic diagnosis is sometimes non-conclusive with a Breast imaging Reporting and Data System (Bi-RaDS) result of 0. Cancer antigen 15-3 (CA15-3) is the most widely used serum tumor marker for breast cancer screening. Platelet distribution width (PDW) is an early indicator of platelet activation. Fibrinogen contributed to angiogenesis and distant metastasis. The aim of this study was to investigate the ability of CA15-3, PDW, and fibrinogen individually or in combination, to distinguish breast cancer from benign breast disease. 200 consecutive patients with breast cancer and 187 patients with benign breast disease were included in this retrospective study. Patients’ characteristics and hematologic tests data at initial diagnosis were collected. The benefit of adding PDW and fibrinogen to a model with only CA15-3 was evaluated as an increased in the area under the curve (AUC) obtained by receiver operating curve (ROC). CA15-3, PDW and fibrinogen are higher in breast cancer patients than in patients with benign breast disease. Single biomarkers had AUC values ranging from 0.687 for fibrinogen to 0.810 for CA15-3. In addition, the combination of PDW, CA15-3, and fibrinogen increased the AUC to 0.900 (0.866-0.928) (p

// Zhi-Yuan Yun 1,* , Na Li 1,* , Xin Zhang 1 , Huan Zhang 1 , Yue Bu 2 , Yuxiang Sun 3 , Tiemin Liu 1,4 , Rui-Tao Wang 1 and Kai-Jiang Yu 2 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China 2 Department of Intensive Care Unit, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China 3 Departments of Pediatrics & Molecular and Cellular Biology, Children’s Nutrition Research Center, Huffington Center on Aging, Baylor College of Medicine, Houston, TX, USA 4 Department of Internal Medicine, Division of Hypothalamic Research, UT Southwestern Medical Center, Dallas, TX, USA * These authors have contributed equally to this work Correspondence to: Rui-tao Wang, email: // Kai-jiang Yu, email: // Keywords : gastric cancer, mean platelet volume, platelet distribution width, diagnosis Received : October 02, 2016 Accepted : February 21, 2017 Published : March 04, 2017 Abstract Activated platelets are involved in cancer development and progression. Mean platelet volume (MPV) and platelet distribution width (PDW) are early indexes of platelet activation. The objectives of this study were to investigate the ability of MPV, PDW and carcinoembryonic antigen (CEA) individually or in combination, to distinguish between gastric cancer and gastric ulcer. The study involved 194 patients with gastric cancer, 191 patients with gastric ulcer, and 185 control subjects. Subjects’ characteristics and hematologic tests data at initial diagnosis were collected. We found that MPV levels are significantly increased and PDW levels are significantly reduced in patients with gastric ulcer and in control subjects compared with those in gastric cancer. When the area under the curve (AUC) was used to analyze control subjects versus gastric cancer, the combination of PDW and CEA exhibited a significantly larger AUC of 0.939 (0.910-0.961) compared with the combination of MPV and CEA ( p = 0.0045). When AUC was used to analyze gastric ulcer versus gastric cancer, PDW alone had the high specificity (98.5%) and high sensitivity (97.4%). In conclusion, combined use of MPV, PDW and CEA can accurately distinguish gastric cancer from gastric ulcer and controls. Further studies in larger samples are warranted.

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.

Background Low bone mineral density (BMD) and left ventricular (LV) diastolic function are associated with heart failure. However, little is known about the association between BMD and LV diastolic function. Hypothesis BMD is independently related to LV diastolic function in women. Methods We conducted a cross-sectional study of 432 women. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic examination. Results BaPWV and the percentage of LV diastolic dysfunction increased with progressive bone loss. Moreover, partial correlation analysis demonstrated that BMD at spine L2–4 and at femoral neck were correlated with baPWV and LV diastolic function parameters after adjusting covariates. Multivariate logistic regression analysis revealed that osteoporosis was independently associated with LV diastolic dysfunction in women. Conclusions Osteoporosis is independently associated with LV diastolic dysfunction in women. A prospective study is needed to elucidate the effects of BMD on cardiac function in women.

Aims Type 2 diabetes (T2DM) is associated with chronic heart failure and cardiomyopathy. Furthermore, low bone mineral density (BMD) predicts incident heart failure. Abnormal diastolic function reflects early changes in cardiac function and plays a key role in the development of heart failure. The purpose of this study was to investigate the association between BMD with left ventricular (LV) diastolic function in men with T2DM. Methods In all, 344 men with T2DM and 331 age-matched control subjects were enrolled. BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic evaluation. Results BMD was lower in men with T2DM than in controls. There were significant differences in the level of parameters reflecting cardiac structure and LV diastolic function between two groups. Moreover, LV diastolic function and structure parameters also showed significant differences as BMD reduced in T2DM group. BMD at femoral neck was correlated with LV diastolic function parameters in T2DM after adjusting for confounding factors. Multivariable logistic analysis revealed that osteopenia and osteoporosis were associated with diastolic dysfunction compared to the control in men with T2DM. However, no association between BMD and LV diastolic function was found in subjects without T2DM. Conclusion Osteoporosis may be an independent factor for LV diastolic dysfunction in men with T2DM. Our data suggested that early detection of abnormal BMD should warrant for early search of undetected LV diastolic dysfunction in diabetic men.

Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced necrosis can be controlled by multiple genes. In this study, we observed that both strands (5p and 3p) of miR-223 were remarkably dysregulated in mouse hearts upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited better recovery of contractile performance over reperfusion period and lesser degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL necroptotic pathway and inflammatory response were suppressed in transgenic hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R-triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically, we identified two critical cell death receptors, TNFR1 and DR6, as direct targets of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and IκB kinase α, two important mediators known to be involved in I/R-induced inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for the treatment of ischemic heart disease.

Gallstones have been linked to dyslipidemia, metabolic syndrome and cardiovascular disease. Arterial stiffness is an indicator of subclinical atherosclerosis. The aim of this study was to prospectively examine the relationship between gallstone disease and arterial stiffness progression in 347 men and 454 women. These subjects were followed for 7 years. Arterial stiffness progression was measured based on increases in brachial-ankle pulse wave velocity. Changes in brachial-ankle pulse wave velocity during the study period were significantly greater in patients with gallstones than in subjects without gallstones. After adjusting for multiple risk factors, gallstone disease was found to be a significant and independent predictor of brachial-ankle pulse wave velocity progression (β=0.189; P

Hypertension (HTN) and osteoporosis are associated with the development and progress of atherosclerosis. However, little research has been conducted to examine the relationship between arterial stiffness and bone mineral density (BMD) in men with HTN. This cross‐sectional study recruited 355 men with HTN and 353 control patients without HTN. Brachial‐ankle pulse wave velocity (baPWV) and BMD measurements were performed. BMD was decreased and baPWV was elevated in patients with HTN compared with control patients (femoral neck [FN] BMD in the HTN and control groups were 0.662±0.195 g/cm(2) and 0.713±0.204 g/cm(2), respectively [P=.001], and baPWV in the HTN and control groups were 1403.3±156.8 cm/s and 1354.8±136.0 cm/s, respectively [P

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for increased cardiovascular disease. Altered hemorheological parameters have also been shown to play a crucial role in atherogenesis. Moreover, increased viscosity is observed in insulin resistance, metabolic syndrome, hypertension, diabetes, ischemic heart disease, and stroke. A recent study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. AIMS This study aimed to investigate the association of WBV with NAFLD. METHODS In this cross-sectional study, we investigated the relationship between WBV and NAFLD in 1329 subjects (962 men and 367 women) in a general health examination. RESULTS WBV at low shear stress was elevated in patients with NAFLD. In addition, the prevalence of metabolic syndrome and NAFLD increased as WBV quartiles increased both in men and in women. Multiple regression analysis further identified WBV as an independent and significant determinant for NAFLD. CONCLUSIONS The findings showed that WBV at low shear stress is increased in NAFLD. Moreover, WBV at low shear stress is independently associated with NAFLD even after adjusting other cardiovascular risk factors.

Background. The gut microbiota is involved in the occurrence and development of chronic liver diseases. Zonulin is considered a marker of intestinal permeability. The purpose of this study was to assess zonulin levels in patients with chronic hepatitis B (CHB), HBV-associated liver cirrhosis (LC), and HBV-associated hepatocellular carcinoma (HCC). Materials and Methods. The study population consisted of 90 HBV-associated HCC patients, 90 HBV-associated LC patients, 90 CHB patients, and 90 healthy subjects. Serum levels of zonulin and AFP were determined. The diagnostic accuracy of each marker was evaluated using receiver operating characteristic (ROC) curve analysis (AUC). Results. Serum zonulin levels were significantly higher in patients with HCC than in patients with LC or CHB or healthy subjects (p<0.001). Moreover, the zonulin levels were increased in the advanced stage of LC and HCC. ROC curve analysis revealed that serum zonulin could be used to differentiate CHB from cirrhosis. In addition, the combination of zonulin and AFP exhibited a significantly larger AUC compared with zonulin or AFP alone. Conclusions. Serum zonulin levels were significantly increased both in LC and in HCC and correlated with the advanced stage of LC and HCC. Moreover, the combination of zonulin and AFP confers significant benefit to diagnostic accuracy in differentiating LC from HCC.

Prostate cancer (PCa) is the second most common cancer in men worldwide. When the disease becomes metastatic, limited treatment strategies exist, and metastatic disease prognoses are difficult to predict. Recently, evidence has emerged, which indicates that small RNAs are detectable in patient fluids, and exosomal small RNA ectopic expression is correlated with the development, progression, and metastasis of human PCa; however, the role of small RNAs in PCa is only partially understood. In this review, we discuss the research status regarding circulating exosomal small RNAs and applications using these small RNAs in PCa particularly looking at metastatic disease. Exosomal small RNAs could be used as potential biomarkers for the early diagnosis, micrometastasis detection, and prognosis of PCa.

Background Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Activated platelets play a key role in tumor growth and tumor metastasis. Platelet distribution width (PDW) is a platelet index, and is altered in patients with malignancies. The aim of this study was to explore whether PDW can effectively predict death outcome of breast cancer patients. Study design The clinical data of 271 breast cancer patients in our hospital between January 2009 and December 2009 were retrospectively analyzed. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. Result There were significant correlations between increased PDW and tumor size, molecular subtype, differentiation grade, and cancer stages (T, N, or TNM). Moreover, survival analysis revealed that the overall survival of patients with PDW > 16.8%, which was significantly shorter than those with PDW ⩽ 16.8%. Multivariate analysis indicated that PDW > 16.8% predicts a poor overall survival of breast cancer patients. Conclusions Elevated PDW may serve as a marker of adverse prognosis in breast cancer. However, these data are preliminary and should be interpreted with caution pending validation by additional clinical and molecular/genomics studies in various populations.

Background Patients with hepatocellular carcinoma (HCC) having pre-existing type 2 diabetes (T2DM) have a poorer prognosis than those without T2DM. Moreover, accumulating evidence reveals that activated platelets play a crucial role in tumor and T2DM. The mean platelet volume (MPV) indicates platelet activation and is altered in malignancies. The present study aimed to investigate the clinical significance of MPV in patients with HCC having T2DM. Methods This retrospective study performed between January 2010 and December 2013 included 331 patients with HCC (165 with T2DM and 166 without T2DM). The overall survival was compared, and the predictors of overall survival were analyzed. Results The patients with T2DM had lower MPV levels than those without T2DM. Furthermore, the MPV levels significantly differentiated T2DM from non-T2DM. In addition, for patients with T2DM, the overall survival was significantly shorter in patients with low MPV levels than in those with high MPV levels. Multivariate analysis identified decreased MPV as an independent prognostic factor for overall survival only in patients with T2DM, but not in those without T2DM. Conclusion Reduced MPV was a prognostic factor for poor outcome in patients with HCC and T2DM.

Esophageal cancer (EC) is the sixth most common cause of death from cancer. Altered mean platelet volume (MPV) levels were found in patients with malignancies.The present study investigated whether MPV can predict the survival in EC patients.The clinical data of 236 consecutive EC patients between January 2009 and December 2009 in our center were retrospectively analyzed. The overall survival rate was estimated using Kaplan-Meier method. Cox proportional hazards models were fitted to model the relationships between patient characteristics and prognosis.Decreased MPV was significantly correlated with tumor location and tumor differentiation (p0.001). Moreover, survival analysis revealed that the overall survival of patients with MPV ⩽ 7.4 fL was significantly shorter than that of those with MPV7.4 fL. Multivariate analysis identified MPV as an independent poor prognostic factor for overall survival.Reduced MPV is associated with worse survival outcome in EC.

Most pancreatic cancer (PC) patients manifest multiple liver metastases at the time of diagnosis. Activated platelets play a key role in tumor growth and tumor metastases. Mean platelet volume (MPV) is a platelet index and is altered in patients with malignancies. This study aimed to evaluate whether MPV can effectively predict death in PC patients with synchronous liver metastases. The clinical data of 411 PC patients with synchronous liver metastases between January 1, 2006 and December 31, 2013 were retrospectively analyzed. Subjects were divided into two groups by MPV levels. Clinicopathological data were collected retrospectively and relationships between MPV levels and clinical parameters were evaluated. Survival analysis was performed. Increased MPV was not significantly correlated with tumor location, tumor size, and CA19.9. The Kaplan-Meier analysis showed that the overall survival of patients with MPV > 8.7 fL was significantly shorter than that of those with MPV ≤ 8.7 fL (log-rank p

Background and Aim Although the influence of cigarette smoking on the incident risk of liver cancer has been determined, the association between smoking and liver cancer mortality remains uncertain. Methods We searched Pubmed, EmBase, and Web of Science databases to obtain eligible studies. Hazard ratio (HR) value and 95% confidential intervals (CI) were pooled by using a random-effects model, and dose–response analyses were conducted to quantify associations between smoking and mortality from liver cancer. Results A total of 27 articles involving four million participants from seven countries by retrieval (published 1986–2014) were finally included. Pooled HR values for liver cancer mortality was 1.45 (95% CI: 1.33–1.59), 1.22 (95% CI: 1.11–1.34) and 1.16 (95% CI: 1.01–1.32) for current, former, and ever smokers, respectively, when compared with nonsmokers. The risk increased by 7.1% (95% CI: 1.4–13.2) for per additional 10 cigarettes per day and by 5.2% (95% CI: 0.02–11.2) for per additional 10 pack-years. In our population recruiting 597 patients with liver cancer, smoking status was further identified as a significant determinant factor of tumor size and serum level of gamma-glutamyl transpeptidase, but not a significant prognostic factor. Conclusions Cigarette smoking, especially current smoking, significantly increased mortality risk from liver cancer.

BACKGROUND The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease and dementia. Increased viscosity is associated with aging, obesity, carotid intima-media thickness, metabolic syndrome, hypertension, diabetes, ischemic heart disease, and stroke. AIMS The purpose of the study was to assess the hemorheological parameters levels in SCI patients. METHODS A cross-sectional study was conducted to evaluate the association between hemorheological parameters and SCI in 1487 subjects (868 men and 619 women) undergoing medical check-up. RESULTS The participants with SCI had higher whole blood viscosity (WBV) levels at low shear rate than those without SCI (10.34 ± 1.77 mPa.s vs. 8.98 ± 0.88 mPa.s; P < 0.001). Moreover, the subjects with a high WBV had a higher prevalence of SCI. Logistic regression analysis revealed that a significant association of WBV levels with the risk of SCI after adjustment for confounding factors (OR: 2.025; 95% CI: 1.750-2.343; P < 0.001). CONCLUSIONS Whole blood viscosity at low shear rate is a novel indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of whole blood viscosity may be helpful to assess the risk of stroke.

Aims Diabetic retinopathy (DR) is the most common complication of type 2 diabetes mellitus (T2DM). Inflammation plays a considerable role in the pathogenesis of T2DM and DR. Emerging evidence revealed that the neutrophil–lymphocyte ratio (NLR) may be a useful marker of cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is an indicator for early atherosclerotic changes. Therefore, this study aimed to investigate the association of NLR with baPWV in patients with DR. Methods In this cross-sectional study, we investigated the relationship between NLR and baPWV in 402 participants. Participants were divided into the following three groups: 133 control subjects without T2DM; 138 diabetic subjects without DR; and 131 patients with DR. Results NLR and baPWV were elevated both in T2DM and in DR. Moreover, compared to T2DM, NLR and baPWV were higher in DR. There was a positive correlation between NLR and baPWV in patients with T2DM and DR after adjusting confounding factors. Multiple linear regression analysis further revealed that NLR was an independent and significant determinant for elevated baPWV (for T2DM, β=0.170; p =0.041; for DR, β=0.188; p =0.022, respectively). Conclusions The findings showed that NLR and baPWV are elevated both in T2DM and in DR. In addition, NLR is independently associated with baPWV. Early detection of abnormal NLR levels may be helpful for the search of subclinical atherosclerosis in patients with T2DM and DR.

NAFLD is an independent risk factor for increased cardiovascular disease. Arterial stiffness is an index of subclinical atherosclerosis. The aims of this study were to examine prospectively the relationship between Non-alcoholic fatty liver disease (NAFLD) and the progression of arterial stiffness.A prospective study of 728 men and 497 women free of hypertension, and diabetes at the baseline were conducted. The subjects were followed for 5 years. The progression rate of arterial stiffness was measured by calculating the increase in brachial-ankle pulse wave velocity (baPWV) the changes of the baPWV (adjusted for age) during the study period was significantly greater in the patients with NAFLD (172.4 ± 42.1 cm/s for men, 95.8 ± 36.7 cm/s for women) than in the subjects without NAFLD (70.3 ± 56.5 cm/s for men, 55.4 ± 42.2 cm/s for women). For the subjects with metabolic syndrome, after adjusting for multiple risk factors, NAFLD was a significant predictor of baPWV progression (for male, β = 0.843; P0.001; for female, β = 0.575; P0.001, respectively). In addition, results were unmodified in subjects without metabolic syndrome.NAFLD was found to be an independent predictor of faster progression of baPWV even after adjusting other cardiovascular risk factors. These prospective data support a pathogenic role for NAFLD in the development of arterial stiffness.

Aim: To explore the value and prospects of the combined vessel resection with reconstruction techniques in space-occupying lesion surgical treatment. Method: We collected and analyzed clinical data of patients received combined with vessel resection and reconstruction techniques surgery in department of hepatobiliary surgery in our hospital from May 2007 to November 2012, and concluded experience in application of vessel resection and artificial vessel reconstruction. Result: A total of 12 cases were collected. 9 of them were pancreatic lesion, and the other 3 were liver Echinococcus granulosus. The average operative time of 12 cases was 6.1 ± 1.8 h, and the average blood loss was 385 ± 202 ml. The average intraoperative portal vein occlusion time was 31 ± 13 min. 1 case suffered intraperitoneal hemorrhage within 48 h after surgery and other 2 suffered pancreatic fistula. All of them were treated and cured; there was no infection, thrombosis and other complications and perioperative deaths turned up before discharge. 4 cases of pancreatic cancer patients after 4, 9, 35 and 37 died of tumor recurrence and metastasis: 1 was lost and the rest are all alive. The follow-up time of these cases was 3 - 58 months with an average level of 22.4 months. Conclusion: Occupying lesions that cannot achieve traditional radical resection due to vessel invasion conventional radical resection may be cured by combining with vessel resection and reconstruction of the lesion resection surgery, and with good prospects worthy of promotion and application of clinic; this technique should be applied to lesion in hepatobiliary system.

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 χ 2 = 3.963, P = 0.047, hazard ratio [ HR ] =1.453, 95% confidence interval [ CI ]: 1.006-2.098), lower albumin (Wald χ 2 = 12.213, P HR = 1.982, 95% CI : 1.351-2.910), tumor size (Wald χ 2 = 8.179, P = 0.004, HR = 1.841, 95% CI : 1.212-2.797), and higher alpha-fetoprotein level (Wald χ 2 = 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 χ 2 = 14.491, P HR = 2.285, 95% CI : 1.493-3.496) and tumor size (Wald χ 2 = 21.662, P 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.

Altered mean platelet volume (MPV) is implicated in several malignancies. However, the clinicopathological significance and prognostic value of MPV in colorectal cancer (CRC) is still elusive. The purpose of this study was to elucidate the predictive significance of MPV in CRC. The retrospective study recruited 509 consecutive CRC 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 509 CRC patients, high MPV levels were detected in 150 (29.5%) patients. Elevated MPV was associated with tumor differentiation (p

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

Septic shock increases vascular permeability, leading to multiple organ failure including cardiac dysfunction, a major contributor to septic death. Podosome, an actin-based dynamic membrane structure, plays critical roles in extracellular matrix degradation and angiogenesis. However, whether podosome contributes to endothelial barrier dysfunction during septic shock remains unknown. In this study, we found that the endothelial hyperpermeability, stimulated by phorbol 12-myristate 13-acetate and thrombin, was accompanied by increased formation of podosome clusters at the cell periphery, indicating a positive correlation between podosome clusters and endothelial leakage. Interestingly, we observed that circulating exosomes collected from septic mice were able to stimulate podosome cluster formation in cardiac endothelial cells, together with increased permeability in vitro/in vivo and cardiac dysfunction. Mechanistically, we identified that septic exosomes contained higher levels of reactive oxygen species (ROS) than normal ones, which were effectively transported to endothelial cells (ECs). Depletion of ROS in septic exosomes significantly reduced their capacity for promoting podosome cluster formation and thereby dampened vascular leakage. Finally, we elucidated that podosome cluster-induced endothelial hyperpermeability was associated with fragmentation/depletion of zonula occludens-1 (ZO-1) at the cell periphery. Our results demonstrate that septic exosomes were enriched with high amounts of ROS, which can be transported to ECs, leading to the generation of podosome clusters in target ECs and thereby, causing ZO-1 relocation, vascular leakage, and cardiac dysfunction.

Circulating exosome holds great potentials as biomarker for diagnosis and prognosis of human cancers. Previously, we have applied small RNA sequencing to identify aberrantly expressed exosomal miRNAs as candidates for diagnostic markers in colon cancer patients. In this validation cohort, plasma derived exosomal miRNA was isolated from 50 early-stage colon cancer patients and 50 matched healthy volunteers. Real-time qRT-PCR revealed that miR-125a-3p, miR-320c were significantly up-regulated in plasma exosomes of the patients with early stage colon cancer. ROC curve showed that miR-125a-3p abundant level may predict colon cancer with an area of under the curve (AUC) of 68.5%, in comparison to that of CEA at 83.6%. Combination of miR-125a-3P and CEA improved the AUC to 85.5%. In addition, plasma exosome level of miR-125a-3p and miR-320c showed significant correlation with nerve infiltration (P 0.05). On the contrary, plasma CEA level is correlated with tumor size, infiltration depth, and differentiation degree (P

Objective Cytokine-induced killer (CIK) cells have important therapeutic effects in adoptive cell transfer (ACT) for the treatment of various malignancies. In this study, we focused on in vitro expansion of CIK cells and their clinical efficacy in combination with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods A total of 64 patients with NSCLC (enrolled from 2011 to 2012), including 32 patients who received chemotherapy alone or with sequential radiotherapy (conventional treatment, control group) and 32 patients who received conventional treatment and sequential CIK infusion (study group), were retrospectively analyzed. The time to progression (TTP), overall survival (OS) and adverse effects were analyzed and the phenotype of lymphocytes in CIK population was also determined by flow cytometry. Results After in vitro expansion, the average percentage of CIK cells was 26.35%. During the 54-month follow up, the median OS and TTP were significantly longer in the study group than in the control group ( P = 0.0189 and P = 0.0129, respectively). The median OS of the ACT ≥ 4 cycles subgroup was significantly longer than that of the ACT P = 0.0316). The percentage of CIK cells in patients who received ≥ 4 cycles of ACT was higher than that in patients treated with P = 0.0376). Notably, CIK cells were difficult to expand in vitro in some patients after the first ACT cycle but became much easier as the treatment cycles increased monthly. Longer treatment interval negatively impacted the expansion of CIK cells. Conclusions Systematic immune levels can be increasingly boosted by reinfusion of ACT. Conventional treatment plus CIK cells is an effective therapeutic strategy to prevent progression and prolong survival of patients with advanced NSCLC.

Renal cell carcinoma (RCC) is the third most common genitourinary cancer. Activated platelets play a pivotal role in cancer development and progression. Altered mean platelet volume (MPV) has been reported in several malignancies. The aim of the present study was to investigate the association of MPV with RCC. The study consisted of 145 patients with RCC, 110 patients with benign renal tumor and 132 healthy control subjects between January 2015 and December 2015. All participants’ clinical and laboratory characteristics at initial diagnosis were collected. The odds ratios (ORs) for RCC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV quartiles. The patients with RCC had decreased pre-operative MPV compared to the patients with benign renal tumor and healthy control subjects. Furthermore, pre-operative MPV was reduced in benign renal tumor compared with healthy control subjects. Surgical tumor resection resulted in a significant increase in MPV levels (8.7 fL vs. 9.0 fL; p = 0.011). After adjusting for other risk factors, the ORs (95% CIs) for RCC in each MPV quartile were 25.725 (7.556–87.585), 7.447 (2.701–20.537), 0.703 (0.245–2.019), and 1.000, respectively. RCC patients have remarkably reduced MPV compared to patients with benign renal tumor and healthy control subjects. Moreover, decreased MPV was independently associated with RCC. Our results suggest that detection of MPV may be useful to assess the risk of RCC.

Background The presence of silent cerebral infarction (SCI) increases the risk of transient ischaemia attack, symptomatic stroke, cardiovascular disease and dementia. Mean platelet volume (MPV) is a surrogate marker of activated platelets and is considered a link between inflammation and thrombosis. In addition, MPV is a risk predictor for cardiovascular disease, stroke and overall vascular mortality. Aims The purpose of the study was to assess the MPV levels in SCI patients. Methods A cross-sectional study was conducted to evaluate the association between MPV and SCI in 2215 subjects (1385 men and 830 women). Results The participants with SCI had higher MPV levels than those without SCI (10.4 ± 1.3 fL vs. 9.2 ± 1.2 fL; P < 0.001). Moreover, the subjects with a high MPV had a higher prevalence of SCI. Multivariate logistic regression analyses revealed that the odds ratios and 95% confidence intervals for SCI according to MPV quartiles were 1.000, 2.131 (1.319–3.444), 3.015 (1.896–4.794), 7.822 (4.874–12.554) respectively (P < 0.001). Conclusion MPV is a novel index for SCI regardless of classical cardiovascular risk factors.

Background and Aims Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for increased cardiovascular disease. The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Recently, the effect of changed blood rheology on atherosclerosis has received attention. A study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. Therefore, this study aimed to investigate the association of WBV with baPWV in patients with NAFLD. Methods In this cross-sectional study, the relationship between WBV and baPWV was investigated in 2032 participants (1035 men and 997 women) with NAFLD in a general health examination. Results Different metabolic parameters were compared across WBV (3/s) quartiles. The mean values of baPWV gradually increased with WBV (3/s) quartiles. Stepwise multiple linear regression analysis revealed that WBV (3/s) is a significant determinant for increased baPWV both in men and in women (for male, β = 0.229; P