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BACKGROUND: Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. OBJECTIVE: We aimed to assess the association between LBM and PHLF in HCC patients. METHODS: PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. RESULTS: The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172–0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). CONCLUSIONS: LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

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.

The application of a sodium laser guide star is the key difference between a modern adaptive optics system and traditional adaptive optics system. Especially in system such as multiconjugate adaptive optics, a sodium laser guide star asterism that is formed by several laser guide stars in a certain pattern is required to probe more atmospheric turbulence in different directions. To achieve this, a sodium laser guide star asterism launching platform is required. In this paper, we introduce the sodium laser guide star asterism launching platform built and tested on the 1.8 m telescope of Gaomeigu Observatory. The platform has two functions: one function is to compare the performance of sodium laser guide stars generated by different lasers at the same place, and the other function is to generate a sodium laser guide star asterism with an adjustable shape. The field test results at the beginning of 2021 verified the important role of the platform, which is also the first time that a sodium laser guide star asterism was realized in China.

The lack of effective pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) is mainly attributed to insufficient research on its pathogenesis. The pathogenesis of TM6SF2-efficient NAFLD remains unclear, resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.Liver samples collected from both NAFLD mouse models and human participants (80 cases) were used to evaluate the expression of TM6SF2 by using western blotting, immunohistochemistry, and quantitative polymerase chain reaction. RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2. Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD. MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models. TM6SF2 overexpression can reduce hepatic lipid accumulation, suggesting a protective role for TM6SF2 in a high-fat diet (HFD). Downregulation of TM6SF2, simulating the TM6SF2 E167K mutation condition, increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis, accompanied by impaired fatty acid oxidation. Owing to the potential effect of TM6SF2 deficiency on lipid metabolism, the application of an acetyl-CoA carboxylase inhibitor (MK-4074) could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.TM6SF2 plays a protective role in the HFD condition; its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism, and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

BackgroundAs 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.MethodsA 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.ResultsCLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables.ConclusionsThe increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.

In this paper, we investigated the impact of the linewidth of a QCW pulsed sodium laser on the brightness performance of a generating sodium laser guide star by using the numerical simulation tool PRS. We compared the field test results with the simulation results for two TIPC’s 30W class sodium guide star lasers and found the results are in good agreement which proves the tool can be used for prediction. Then, we used the tool to study the influence of D2b repumping and different linewidths from 10MHz to 1GHz on the coupling efficiency and the photon return flux. For the TIPC’s QCW pulsed solid-state laser, when the on-sky power density is 1 W/m2, the coupling efficiency is 79.6 (photons/s/W/(atoms/m2)) without D2b repumping, however, the value is up to 213.3 (photons/s/W/(atoms/m2)) with 15% D2b enabled and is increased by 168% than the value without D2b; when the power density reaches 10 W/m2, the coupling efficiencies without D2b and with 15% D2b are 66.6 and 233.6 (photons/s/W/(atoms/m2)), respectively. The results show that for the QCW pulsed laser, D2b repumping is necessary. With D2b enabled, if the spectral linewidth is too wide or too narrow, the photon return flux will be adversely affected. The return flux of 60MHz is 52.5% higher than that of 1GHz, while the return flux of 300MHz is 37.8% higher than that of 10 MHz when the laser power is 100W.

Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer’s disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L. plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αβ levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD.

Enterocyte damage and subsequent microbial translocation drive neuroinflammation in the pathogenesis of Alzheimer's disease (AD). Human ileal bile acid binding protein (I-BABP) and intestinal fatty acid binding proteins (I-FABP) are the indicators of enterocyte damage. Lipopolysaccharide-binding protein (LBP) is an indirect marker of microbial translocation. The activation of peripheral innate immune cells plays a crucial role in modulating AD progression. Galectin-9 is a versatile immunomodulatory molecule. The purpose of this study was to determine I-FABP, I-BABP, LBP, and galectin-9 levels in MCI and AD and investigate the relationship between I-FABP, I-BABP, LBP and galectin-9. In this study, I-FABP, I-BABP, LBP, and galectin-9 levels were measured using ELISA assay in 115 AD patients, 115 MCI patients, and 115 non-demented control subjects. Increased I-BABP and galectin-9 were observed in MCI and AD patients. Furthermore, AD patients had higher I-BABP and galectin-9 levels compared with MCI patients. However, I-FABP and LBP in three groups had no difference. I-BABP levels were positively correlated with galectin-9, after adjusting confounding factors (r = 0.409, p 0.001). In addition, multivariate analysis revealed that increased I-BABP and galectin-9 levels were significantly associated with reduced mini-mental state examination (MMSE) score. In conclusion, galectin-9 is correlated with I-BABP after adjusting confounding covariates. Moreover, increased I-BABP and galectin-9 in MCI and AD are significant factors for reduced MMSE score. Further studies are needed.

OBJECTIVE Increased permeability and changes in gut microbiota contributed to the pathogenesis of Alzheimer's disease (AD). Zonulin is a key modulator that regulates intestinal barrier function. Peripheral platelet alterations have been involved in AD pathology. C-type lectin-like receptor 2 (CLEC-2) is a receptor on the platelet surface for activation. The purpose of this study was to determine zonulin and CLEC-2 levels in mild cognitive impairment (MCI) and AD, and investigate the relationship between zonulin and CLEC-2. METHODS In this study, CLEC-2 and zonulin levels were measured using ELISA assay in 110 AD patients, 110 MCI patients, and 110 non-demented control subjects. RESULTS Increased CLEC-2 and zonulin levels were observed in MCI and AD patients. Furthermore, AD patients had higher CLEC-2 and zonulin levels compared with MCI patients. In addition, CLEC-2 levels were positively correlated with zonulin levels, after adjusting confounding factors (r = .592, P

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

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: 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.

Multiple synthetic beacons are required for atmospheric-turbulence compensation in an extended-field-of-view multi-conjugate adaptive optics (MCAO) telescope. In this paper, we report on the first successful implementation of a microsecond-pulse sodium guidestars constellation laser system, based on a small angle precise polarized combining and splitting technology. At Lijiang Observatory of China, four-ways ∼20 W yellow laser beam with kHz repetition-rate and hundred-μs pulse width were projected into the sky through one small-aperture launching telescope, and generated a distinctive four-point grouping on a field of view of 40″ with variable configurations of linear, parallelogram, rhomboid and square. The sodium return signal could easily avoid Rayleigh light interference by the pulse synchro controlling technology delivering a higher spatial resolution. Moreover, the increase in return photons for alternated circularly and alternated linearly polarized light has been investigated. We believe that the above results could serve as a future reference for the MCAO system on large-aperture telescopes worldwide.

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: Postoperative sepsis in cancer patients becomes a major problem at present, but the efficiently prognostic biomarkers are limited. The present study was sought to evaluate the prognostic relevance of absolute lymphocyte counts (ALCs) in cancer patients with postoperative sepsis, which might help patients to get early treatment and improve their prognosis.Methods: Retrospective study was conducted under 368 cancer patients with postoperative sepsis who were admitted in ICU of two Chinese tertiary care hospitals from January 1, 2016 to December 31, 2017. ALCs were daily collected during the first week after being enrolled in the study. The primary outcomes of the study included 28-day and 90-day mortalities, while the secondary outcomes were hospital and ICU length of stay.Results: The absolute lymphocyte counts on day 3 were reduced in the survivors comparing with those in non-survivors. Statistically, the significantly decreased 28-day and 90-day survival rates were detected in the patients with severe and moderate lymphopenia, compared to those with no lymphopenia. These present results were consistently found and evidently confirmed in the two different hospitals.Conclusions: In accordance with the day-4 lymphopenia prediction of sepsis diagnosis, this present study revealed that lymphopenia on the day 3 after the diagnosis of sepsis was able to predict the early mortality in postoperative cancer patients. Earlier monitoring and management of lymphopenia may be needed for cancer patients with postoperative sepsis.

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.

// 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.

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

// 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.

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.