High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non–small cell lung cancer(NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age ≥ 65 years(P = 0.011), smoking status(P = 0.009), intracranial symptoms(P = 0.022), clinical T category(P = 0.010), clinical N category(P = 0.003), increased partial thromboplastin time(P < 0.001), and platelet count(P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration(median, 17.3 months versus 11.1 months; P ≤ 0.001). A similar result was observed for platelet counts(median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases(R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Chimeric antigen receptor-engineered T-cell therapy for liver cancer

Background: Chimeric antigen receptor-engineered T-cell(CAR-T) therapy is a newly developed immunotherapy used in the treatment of cancers. Because CAR-T therapy has shown great success in treating CD19-positive hematological malignancies, its application has been explored in the treatment of solid tumors, such as liver cancer. In this review, we discuss the immune characteristics of liver cancer, the obstacles encountered during the application of CAR-T therapy, and preclinical and clinical progress in the use of CAR-T therapy in patients with liver cancer.Data sources: The data on CAR-T therapy related to liver cancers were collected by searching Pub Med and the Web of Science databases prior to December 2017 with the keywords "chimeric antigen receptor","CAR-T", "liver cancer", "hepatocellular carcinoma", and "solid tumor". Additional articles were identified by manual search of references found in the primary articles. The data for clinical trials were collected by searching Clinical Trials.gov.Results: The liver has a tolerogenic nature in the intrahepatic milieu and its tumor microenvironment significantly affects tumor progression. The obstacles that reduce the efficacy of CAR-T therapy in solid tumors include a lack of specific tumor antigens, limited trafficking and penetration of CAR-T cells to tumor sites, and an immunosuppressive tumor microenvironment. To overcome these obstacles, several strategies have emerged. In addition, several strategies have been developed to manage the side effects of CAR-T, including enhancing the selectivity of CARs and controlling CAR-T activity. To date, no clinical trials of CAR-T therapy against HCC have been completed. However, preclinical studies in vitro and in vivo have shown potent antitumor efficacy. Glypican-3, mucin-1, epithelial cell adhesion molecule, carcinoembryonic antigen, and other targets are currently being studied.Conclusions: The application of CAR-T therapy for liver cancer is just beginning to be explored and more research is needed. However, we are optimistic that CAR-T therapy will offer a new approach for the treatment of liver cancers in the future.

腺样体切除术后阻塞型睡眠呼吸暂停低通气综合征患儿骨龄和血清骨钙素的变化

目的探讨腺样体切除术对阻塞型睡眠呼吸暂停低通气综合征(OSAHS)患儿术后气道阻塞改善、骨龄及骨钙素水平改变情况。方法选取2017年10月—2019年3月徐州医科大学附属淮安医院就诊的OSAHS患儿85例。根据呼吸暂停低通气指数(AHI)分为轻度组19例,中度组46例,重度组20例;另纳入30例健康儿童作为对照组。监测腺样体切除术术前(T_(0))和术后6月(T_(1))OSAHS患儿AHI、最低血氧饱和度(MiniSO_(2))、血氧饱和度下降指数(ODI4)、血氧饱和度<90%百分比(TS90%)、Epworth嗜睡度量表(ESS)、骨钙素及骨龄改变情况。结果 T1时组内比较,OSAHS患儿AHI、ODI4、TS90%和ESS降低(P <0.05),骨钙素水平升高(P <0.05),△骨龄-实际年龄降低(P <0.05)。亚组分析可见除轻度组MiniSO_(2)外,各组OSAHS患儿的呼吸指标均改善(P <0.05)。T0时轻度组、中度组、重度组骨钙素水平均低于对照组(P <0.05),而△_(骨龄-实际年龄)水平高于对照组(P <0.05)。相关性分析提示△骨钙素与△AHI、△ODI4和△TS90%(r=-0.654、-0.706和-0.622,均P <0.05)呈负相关。结论腺样体切除术可以改善OSAHS患者气道阻塞症状和骨骼发育情况。

Effects of Copper-phenanthroline on Pentachlorophenol-induced Adaptation and Cell Death of Escherichia coli

Objective To evaluate the effects of copper-phenanthroline （CuOP） on pentachlomphenol （PCP）-induced adaptation and cell death of Escherichia coli. Methods Bacterial growth and adaptation to PCP were monitored spectrophotometrically at 600 nm. Inactivation of bacterial cells was determined from colony count on agar dishes. Cellular ATP content and accumulation of PCP were assessed by chemiluminescence and HPLC analysis respectively. The formation of PCP-Cu-OP complex was shown by UV-visible spectra. Results Escherichia coli （E. coli） could adapt to PCP, a wood preservative and insecticide used in agriculture. The adaptation of E. coli to PCP prevented its death to the synergistic cytotoxicity of CuOP plus PCP and declined cellular accumulation and uncoupling of oxidative phosphorylation of PCP. Furthermore, CuOP and PCP neither produced reactive oxygen species （ROS） nor had a synergistic effect on uncoupling of oxidative phosphorylation in E. coli. The synergistic cytotoxicity of CuOP and PCP in E. coli might be due to the formation of lipophilic PCP-Cu-OP complex. Conclusion Our data suggested that adaptation of E. coli to PCP decreased the synergistic effects of CuOP and PCP on prokaryotic cell death due to the formation of lipophilic PCP-Cu-OP complex, but it had no effect on the uncoupling of oxidative phosphorylation and production of reactive oxygen species in E. coli.

A topology approach to overcome the pore size/volume trade-offs for autonomous indoor humidity control

Autonomous indoor humidity control is gaining more and more attention but is limited by the trade-offs among pore volume,pore size and water stability of water adsorbents.We solve this problem by using a unique coordination network topology combined with hydrolytically stable M(Ⅲ)carboxylate clusters.By extending the ligand length from 9.0 to 11.2 and 13.7?,the pore volume significantly increases from 0.99 to 1.40 and 1.78 cm^(3)g^(-1),which proportionally increases the saturated water adsorption capacity.Meanwhile,the pore size slightly increases from 10.4 to 11.0 and 13.5A,which restricts the isotherm inflection pressure and hysteresis width to meet the requirement of indoor humidity control.Large single-crystals suitable for Xray diffraction studies were obtained by using Fe(Ⅲ)salts,while isostructural frameworks with sufficiently high water stabilities were synthesized by using Cr(Ⅲ)salts,which offer record working capacity of 0.90 and 1.10 g g^(-1)for indoor humidity control.

Local Weak Hydrogen Bonds Significantly Enhance CO_(2)Electroreduction Performances of a Metal-Organic Framework

Technological application of the electrochemical reduction of CO_(2)relies on efficient electrocatalysts.We demonstrate that the introduction of amino groups alongside the porphyrin cobalt centers in a metal-organic framework(MOF)can dramatically accelerate the electrochemical CO_(2)reduction performance.A classic cobalt porphyrin-based MOF showing moderate CO_(2)-to-CO electroreduction performance(turnover frequency[TOF]=0.20 s^(−1),Faradic efficiency[FE]=47.4%)is modified.By molecular design of the porphyrin-based ligand,amino groups are introduced alongside the cobalt center,giving remarkably enhanced CO_(2)-to-CO electroreduction performance as high as FE 99.4%,current density 7.2 mA cm^(−2),and TOF 21.17 s^(−1),in a nearneutral aqueous solution at a low overpotential of 525 mV.Density functional theory calculations showed that the prepositioned amino groups,although located not sufficiently close to the active center,serve as hydrogen-bonding donors to stabilize the intermediate Co-CO_(2)adduct and impede the formation of Co-H_(2)O adduct,which not only promotes the CO_(2)reduction reaction but also restrains the hydrogen evolution reaction.

MiR-27a Promotes Hepatocellular Carcinoma Cell Proliferation Through Suppression of its Target Gene Peroxisome Proliferator-activated Receptor γ

Background： MicroRNAs （miRNAs） function as essential posttranscriptional modulators ofgene expression, and are involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs are deregulated in hepatocellular carcinoma （HCC）. This study aimed to investigate the role of miR-27a in the development of HCC. Methods： The expression of MiR-27a was measured by quantitative real-time polymerase chain reaction （qRT-PCR）. 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide was used to examine changes in the viability of HepG2, Bel-7402, Bel-7404 hepatoma cell lines associated with up-regulation or down-regulation of miR-27a. A dual-luciferase activity assay was used to verily a target gene ofmiR-27a, lmmunohistochemistry, qRT-PCR, Western blotting analysis, and cell cycle and apoptosis flow cytometric assays were used to elucidate the mechanism by which miR-27a modulates liver cancer cell proliferation. Results： The expression of miR-27a was significantly increased in HCC tissues and HepG2, Bel-7402, Bel-7404 hepatoma cell lines （P 〈 0.05）. We also found that the down-regulation of miR-27a in HepG2 cells dramatically inhibited proliferation, blocked the G1 to S cell cycle transition and induced apoptosis （P 〈 0.05）. In addition, miR-27a directly targeted the 3＇-untranslated region of peroxisonae proliferator-activated receptor y （PPAR-γ）, and ectopic miR-27a expression suppressed PPAR-γ expression on the mRNA and protein levels. The rosiglitazone-induced overexpression of PPAR-γ attenuated the effect of miR-27a in HCC cells. Conclusions： Our findings suggested that miRNA-27a promoted HCC cell proliferation by regulating PPAR-γ expression. MiR-27a may provide a potential therapeutic strategy for HCC treatment.

Multistep evolution from a metal–organic framework to ultrathin nanosheets

Two-dimensional (2D) materials and ultrathin nanosheets have attracted tremendous research interests [1-4]. Exfoliation of porous coordination polymers (PCPs) or metal-organic frameworks (MOFs) with 2D coordination structures is emerging as a viable strategy for preparation of new types of 2D materials [5-8]. The relatively weak bonding within and strong interactions between 2D coordination networks are the main problems for successful exfoliation [9]. Pretreatments of the layered MOFs to expand the interlayer distances can be helpful [10-12]. Capturing the exfoliation intermediates and visualizing their structures are valuable for understanding the exfoliation mechanism and confirming the structures of the final 2D materials [11,12].

An Au(Ⅰ)-based coordination/hydrogen-bond hybrid open framework for luminescence sensing of temperature and benzene

Molecule-based porous materials sustained by coordination and/or covalent bonds have been extensively investigated[1,2].Hydrogen bonds and weaker supramolecular interactions can also serve as the links for porous frameworks,but successful examples showing permanent porosity and especially high stability are still rare[3,4].Cooperation of multiple weak interactions is the most effective strategy to enhance the stability of porous molecular crystals[5].

Relationship between Free Fatty Acid Spectrum,Blood Stasis Score,and Macroangiopathy in Patients with Type 2 Diabetes

Objective:Our aim was to investigate the correlation between free fatty acid(FFA) spectrum, blood stasis(BS) score, and macroangiopathy in type 2 diabetic patients with or without BS, as well as the possible relationship between BS and lipotoxicity. Methods: A total of 50 type 2 diabetes(T2D) patients with or without BS were enrolled from June to December 2014 in Shenzhen Traditional Chinese Medicine(TCM) Hospital, with 25 patients allocated to each of two groups. Basic information, BS score, blood glucose, blood lipids, etc., were measured for each patient. In addition, we tested the levels of interleukin(IL)?6, tumor necrosis factor α(TNF?α), and IL?18 with enzyme?linked immunosorbent assay. The macroangiopathy status of patients in the two groups was examined by color ultrasound and all factors related to BS scores were analyzed. Gas chromatography?mass spectrometry was used to explore the difference in the serum FFA spectra between the two different groups. In addition, the relationship between FFA spectra, BS scores, and macroangiopathy was analyzed. Results: BS scores, total cholesterol(TC), total triglyceride(TG), low?density lipoprotein cholesterol, IL?6, TNF?α, IL?18, carotid and femoral artery plaque, carotid intima?media thickness, carotid plaque area, and femoral artery plaque area were all significantly increased in T2D patients with BS syndrome(P < 0.05). A positive correlation was observed between age, duration of diabetes, carotid intima?media thickness, carotid plaque area, femoral artery plaque area, and BS score(P < 0.05). A total of 21 fatty acids were found in the serum, and total FFA(TFFA), saturated fatty acid(SFA), lauric acid(C12:0), palmitic acid(16:0), stearic acid(C18:0), arachidonic acid(C20:4n6), behenic acid(C22:0), and lignoceric acid(C24:0) scores were all found to contribute to the difference between FFA spectrums of the two groups; of the fatty acids, C12:0, C16:0, C18:0, C22:0, TFFA, and SFA positively correlated with BS scores as evaluated by Pearson's or Spearman's correlation analysis(P < 0.05). Only SFA entered the regression equation in the multiple linear regression analysis. C12:0, C16:0, C18:0, C20:4n6, TFFA, and SFA were positively correlated with carotid plaque area, whereas linoleic acid(C18:3n3), Cis?5, 8, 11, 14, and 17?eicosapentaenoic acids(C20:5n3) were negatively correlated(P < 0.05). C16:0 was positively correlated with the femoral artery plaque area and C18:3n3, cis?4, 7, 10, 13, 16, and 19?docosahexaenoic acids(C22:6) and nervonic acid were negatively correlated(P < 0.05). Conclusion: Serum FFA spectra were significantly different between T2D patients with BS and those without, and long?chain SFA made the greatest contribution. Serum FFA spectra were correlated with BS scores and diabetic macroangiopathy, which means that lipotoxicity and BS are correlated in T2D.

Partial Order-Disorder Transformation of Interpenetrated Porous Coordination Polymers

Controlling interpenetration and flexibility behaviors is intriguing and fundamental for porous coordination polymers.We report exceptional interpenetration behaviors involving controllable partial order–disorder structural transformations.A new bis-benzotriazolate ligand(NaH2sbbta)with a twisted and anionic backbone was designed and synthesized.The solvothermal reaction of ZnCl_(2) and NaH_(2)sbbta yielded(Et_(2)NH_(2))_(3)[Zn_(5)Cl_(4)(sbbta)_(3)]·6DEF(2)possessing two-fold interpenetrated anionic pcu networks with symmetry,shape,and charge different from the known analogues.More interestingly,powder and single-crystal X-ray diffractions showed that 2 can undergo solvent-induced structural transformation to form a noninterpenetrated anionic pcu network with larger pores(1).Consequently,1/2 can selectively adsorb/exchange cationic dyes fromneutral and anionic dyes with tunable size selectivity.However,since the transformations are reversible without obvious change of crystal sizes,the network that disappeared in X-ray crystallography should be mainly disordered rather than decomposed.Further,the structural transformations can be suppressed by thermal decomposition/removal of Et_(2)NH_(2)^(+)/Et_(2)NH.Computational simulations indicate that the ordered and disordered structures are stabilized by relatively large and small solvent molecules,respectively.