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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.

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

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.

// 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.

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.

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.

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

// 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.

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.

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.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5′-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.

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.

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.

// 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.

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.

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. 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.

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: Prostate cancer (PCa) represents the second most commonly diagnosed malignancy and the sixth leading cause for cancer related death among men worldwide. Although use of the prostate specific antigen (PSA) as a diagnostic marker has improved the detection and management of PCa, low specificity and sensitivity has limited its clinical efficacy. Moreover, elevated PSA is frequently observed in benign prostate hyperplasia (BPH). Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used indicators of platelet activation. The purpose of current study was to investigate the ability of PSA, MPV, and PDW individually or in combination, to differentiate PCa from BPH. Materials and Methods: This study included 100 patients with PCa and 108 patients with BPH. We collected all participants’ clinical and laboratory characteristics. The benefit of adding MPV and PDW to a model with only PSA was evaluated as an increased in the area under the curve (AUC) obtained by receiver operating curve (ROC). Results: PCa patients had reduced MPV and elevated PSA and PDW levels compared to BPH patients. Single biomarkers had AUC values ranging from 0.683 for PDW to 0.865 for PSA. Moreover, the combination of PSA, MPV, and PDW increased the AUC to 0.935 (0.892-0.964) (p

Gallbladder cancer (GBC) represents the most common biliary tract malignancy. Activated platelets play an essential role in cancer development and progression. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used indexes of activated platelets in clinical practice. The aim of the current study was to investigate the association of MPV and PDW with GBC. 104 GBC patients and 109 normal control subjects were entered in this study between January 2015 and December 2015. We collected all participants’ clinical and laboratory characteristics at initial diagnosis. The odds ratios (ORs) for GBC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV and PDW quartiles. MPV levels were markedly lower and PDW levels were remarkably higher in GBC patients than control subjects. A significant correlation between PDW and lymph node metastasis was detected. In addition, after adjusting for other risk factors, the ORs (95% CIs) for GBC in each MPV quartile were 5.117 (1.939-13.506), 2.444 (0.917-6.516), 3.718 (1.381-10.007), and 1.000, respectively. The ORs (95% CIs) for GBC in each PDW quartile were 1.000, 2.063 (0.825-5.162), 3.070 (1.108-8.507), and 12.108 (4.243-34.553), respectively. In conclusion, decreased MPV and elevated PDW were independently associated with GBC. Our findings suggest that MPV and PDW are available parameters for early detection of GBC.