Radiotherapy for Lowly Malignant Cranial Inflammatory Myofibroblastic Tumor Accompanied with Intracranial Invasion:Case Report and Literature Review

Inflammatory myofibroblastic tumor(IMT) is rare in clinical practice.As its treatment mainly involves surgery,radiotherapy alone is seldom reported in literature.Here we report a case of lowly malignant cranial IMT with intracranial invasion in a female patient. As surgery was not suitable,intensity modulated radiation therapy(IMRT) was administered.After radiotherapy,the cranial lesions tended to show efficacy.

Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Telomerase-related advances in hepatocellular carcinoma:A bibliometric and visual analysis

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,and overall publication count,while Zucman-Rossi J ranked first in citation count.The five most popular journals were the World Journal of Gastroenterology,Hepatology,Journal of Hepatology,Oncotarget,and Oncogene,while Nature Genetics,Hepatology,and Nature Reviews Disease Primers had the most citations.We extracted 2293 keywords from the publications,120 of which appeared more than ten times.The most frequent were HCC,telomerase and human telomerase reverse transcriptase(hTERT).Keywords such as mutational landscape,TERT promoter mutations,landscape,risk,and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years.CONCLUSION Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Ferroptosis-induced anticancer effect of resveratrol with a biomimetic nano-delivery system in colorectal cancer treatment

Ferroptosis is a novel form of programmed cell death impelled by iron-dependent lipid peroxidation,which may be a potential strategy for cancer therapy.Here we demonstrated for the first time that Resveratrol(RSV),a traditional Chinese medicine(TCM)chemical monomer,could effectually inhibit the growth of colon cancer cells through the ROS-dependent ferroptosis pathway.Mechanistically,RSV evoked the increase of reactive oxygen species and lipid peroxidation in colorectal cancer cells,and eventually lead to ferroptosis.Furthermore,RSV could promote ferroptosis by downregulating the expression of the channel protein solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).To improve the delivery efficiency of RSV,a biomimetic nanocarrier was developed by coating RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol)(PCL-PEG)nanoparticles with erythrocyte membrane(RSV-NPs@RBCm).The RSV-NPs@RBCm provide the possibility to escape macrophage phagocytosis and have a long circulation effect.In addition,when coupled with a tumor-penetrating peptide iRGD,which could trigger enhanced tissue penetration tumor-specifically,the delivery of RSV-NPs@RBCm into tumors would be significantly improved results from the in vivo study demonstrated an excellent treatment efficacy for CRC.Altogether,our study highlighted the therapeutic potential of RSV as a ferroptosis-inducing anticancer agent and when loaded into a biomimetic nanoplatform,it might pave the way for the application of RSV loaded nanosystems for colorectal cancer treatment.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fasciculation with Muscle Ultrasound

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

基于里氏硬度的岩石拉、压强度预测模型研究

单轴抗压强度和抗拉强度是采矿、隧道、边坡、水利、交通等工程设计领域中重要的岩石力学参数,为了降低测试的时间和成本,便于现场估计岩石拉、压强度,本研究基于里氏硬度探索新的无损间接测量岩石拉、压强度方法。通过室内试验获得岩石里氏硬度、单轴抗压强度、劈裂抗拉强度等参数,分析各参数的相关性并得出经验回归公式。试验结果表明:选用的6种岩石的里氏硬度与单轴抗压强度和抗拉强度呈现正相关且相关性显著,里氏硬度与单轴抗压强度间以幂函数关系显著,里氏硬度与抗拉强度间以线性函数关系显著。此外,通过里氏硬度计算岩石单轴抗压强度和抗拉强度的结果误差在15%范围内,与文献中施密特回弹值和波速计算岩石拉、压强度35%误差相比,精度显著提高。里氏硬度测试仪有便捷、快速、低成本、可现场试验的优点,可作为相应地区工程间接获取岩石拉、压强度的测试方法。

Epidemiologic characteristics and risk factors associated with overall survival for patients with mucinous colorectal cancer:A population-based study

BACKGROUND Mucinous adenocarcinoma(MC)has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years.However,data about its epidemiologic and prognostic characteristics are limited.Therefore,patient data extracted from the National Cancer Institute’s Surveillance,Epidemiology,and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC.AIM To determine the epidemiologic and clinicopathological characteristics of MC.METHODS The incidence trend of MC was calculated through the Joinpoint Regression Program.Cox regression analyses were performed to identify prognostic factors associated with overall survival(OS).A nomogram was established to predict the survival probability of individual patients with MC.RESULTS We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018.Rates of MCs in patients aged≤50 years decreased 2.27%/year during 2000-2018.The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018,while the incidence in other anatomic subsites continued to decrease.On multivariable Cox analyses,age,race,tumor site,T stage,N stage,M stage,surgery,and chemotherapy were associated with OS.A nomogram was developed based on these factors,and the area under the curve for 1-year,3-year,and 5-year OS in the training cohort was 0.778,0.778,and 0.768,respectively.CONCLUSION Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix.A nomogram predicting the survival probability of patients with MCs showed good performance.

Small-molecule amines:a big role in the regulation of bone homeostasis

Numerous small-molecule amines(SMAs)play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or biomaterials.On the one hand,SMAs promote bone formation or inhibit bone resorption through the regulation of key molecular signaling pathways in osteoblasts/osteoclasts;on the other hand,owing to their alkaline properties as well as their antioxidant and anti-inflammatory features,most SMAs create a favorable microenvironment for bone homeostasis.However,due to a lack of information on their structure/bioactivity and underlying mechanisms of action,certain SMAs cannot be developed into drugs or biomaterials for bone disease treatment.In this review,we thoroughly summarize the current understanding of SMA effects on bone homeostasis,including descriptions of their classifications,biochemical features,recent research advances in bone biology and related regulatory mechanisms in bone regeneration.In addition,we discuss the challenges and prospects of SMA translational research.

180例肾移植患者他克莫司血药浓度监测

目的研究肾移植患者术后不同时间段他克莫司(FK506)血药浓度的监测情况,为临床安全合理使用FK506提供参考。方法以180例肾移植患者为研究对象,分析术后时间、用药剂量、患者性别、年龄及CYP3A5基因多态性等因素与FK506血药浓度的关系。结果肾移植患者手术1个月后,FK506的用药剂量、血药浓度随着术后时间的延长而逐渐降低,血药浓度的个体差异较大;在术后0～7 d,女性患者血药浓度高于男性(P<0.05),其他时间段内,性别对患者用药剂量、血药浓度的影响差异无统计学意义;在术后的同一时间段中,高龄组(年龄>45岁)患者的用药剂量均略低于低龄组(年龄16～45岁),其中3～6个月内差异有统计学意义(P<0.05)。CYP3A5*3基因多态性对肾移植患者FK506血药浓度影响较大,在术后的同一时间段中,CYP3A5*1*1型患者FK506用药剂量显著高于CYP3A5*1*3型和CYP3A5*3*3型患者(P<0.05),而CYP3A5*1*1型患者血药浓度显著低于CYP3A5*1*3型和CYP3A5*3*3型患者(P<0.05)。结论 FK506血药浓度监测和基因多态性检测可降低免疫过度、不足和药物不良反应的发生,有利于提高移植肾的长期存活率。

Research on the Controllability of Software Networks Based on the Source-Driven Model

The complexity of software system has been increasing with software evolution, which affects the stability of software structure. Most of the existing measurement methods focus on the analysis of the macro-characteristics of the network topology, but lacked a certain depth and expansion to explore the nature of the complexity of the software structure, for this purpose, the complex network control theory was applied to the study of software network controllability. Firstly, the Source-Driver (SD) model was established based on the system control theory, the driver node sets were obtained by the minimum input theorem in the control process of software network topology;Then the relationship between the degree and center degree, the relationship between the in-degree and the out-degree of the software network topology were further analyzed owing to the non-uniqueness of the driver node sets;Finally, the values of the four indicators in the software system were compared. Experimental results show that the driver node sets in the software networks are mainly composed of nodes with low degree values, but it does not mean that the nodes whose in-degree values and out-degree values are also low;The action on control nodes and driver nodes are not random, the controllability of the driver nodes is closely related to the in-degree, when selecting the driver node sets, the network topology characteristics should be considered comprehensively, and the nodes with high degree and center degree are the first choice. The results have important guiding significance for the control, maintenance and redesign of software architecture.

基于YOLOv3框架的高分辨电镜图像原子峰位置检测

高分辨电镜图像中原子峰位置的检测具有十分重要的现实意义,通过精确定量化原子峰位置可以分析物质在微观尺度上的结构形变、电极化矢量分布等重要信息.近年来深度学习技术在图像目标检测领域取得了巨大突破,这一技术可用在高分辨电镜图像处理上,因为原子位置的检测可以看作是一个目标检测问题.本文利用先进的机器学习方法,通过制作高质量原子图像样本集,使用YOLOv3目标识别框架对原子图像进行自动检测,达到预期效果,实现了深度学习技术在高分辨电镜图像处理领域的应用.该方法的运用有望突破自动处理动态、大量电镜图片的瓶颈问题.

基于卷积神经网络的滑动窗口算法在高分辨电镜图像中的应用

原子峰位置的精确定位、原子像绝对强度的标定是利用原子分辨电子显微像确定材料结构的重要前提。近年来快速发展的深度学习技术在计算机视觉和目标检测领域都取得了极大的成功,受此启发,本文建立了针对单原子图像的卷积神经网络。同时并构建了含有大量单原子图像的训练数据集,用于这一卷积神经网络的训练,实现了对单原子图像的可靠检测。利用训练完成的卷积神经网络改进滑动窗口算法,实现了在原子位置检测效果上的明显提升。

Autophagy and multidrug resistance in cancer

Multidrug resistance(MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence.Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.

弛豫铁电体弥散相变与热滞效应的伊辛模型

弛豫铁电体材料在通讯、传感、超声、能量转换、航空航天等领域具有重要的应用.与正常铁电体不同,弛豫铁电体在冷却过程中出现弥散相变,体系的宏观极化不会突然产生,而是出现纳米极性微区,体系的宏观晶体对称性没有明显的变化.如何理解弥散相变及其与内部机制之间的相互影响是一个重要的问题.本研究基于伊辛模型(Ising model),对自旋变量(在研究中视为电偶极子)引入能量势阱的作用,并计算了这一系统的相变过程.结果表明这一改进的伊辛模型使极化率的相变曲线显著变缓,呈现出具有弥散相变的弛豫体特性.研究显示,弛豫体现象出现的一个重要原因是系统内部偶极子受到势阱限制而出现反转受阻,从而使极化率偏离常规铁电体.利用这一改进的伊辛模型进一步研究了弛豫铁电体的热滞效应,分析了热滞的起源,并与实验结果进行了对比分析,明确了弛豫体弥散相变和热滞的物理机制.

A Mobile Localization Strategy for Wireless Sensor Network in NLOS Conditions

The problem of mobile localization for wireless sensor network has attracted considerable attention in recent years. The localization accuracy will drastically grade in non-line of sight(NLOS) conditions. In this paper, we propose a mobile localization strategy based on Kalman filter. The key technologies for the proposed method are the NLOS identification and mitigation. The proposed method does not need the prior knowledge of the NLOS error and it is independent of the physical measurement ways. Simulation results show that the proposed method owns the higher localization accuracy when compared with other methods.

Activation of autophagy in the retina after optic nerve crush injury in rats

AIM: To investigate the activation of autophagy in rat retina after optic nerve crush(ONC) and evaluate its relationship with apoptosis of retinal ganglion cells(RGCs).METHODS: The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. RESULTS: p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3 I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. CONCLUSION: Possible activation of autophagy in RGCs after ONC;autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.

Relationship between Renalase Expression and Kidney Disease： an Observational Study in 72 Patients Undergoing Renal Biopsy

The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 （Bcl-2） expression was investigated in patients （chronic nephritis, primary nephrotic syndrome or other kidney disease） that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining （PAS） and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bel-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee＇s grade Ⅲ than in those with Lee＇s grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

Identification and validation of tumor microenvironment-related lnc RNA prognostic signature for uveal melanoma

AIM:To investigate the role of tumor microenvironment(TME)-related long non-coding RNA(lncRNA)in uveal melanoma(UM),probable prognostic signature and potential small molecule drugs using bioinformatics analysis.METHODS:UM expression profile data were downloaded from the Cancer Genome Atlas(TCGA)and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration.The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis(ss GSEA)method,and the immune cell infiltration of a single specimen was evaluated.Finally,the specimens were divided into high and low infiltration groups.The differential expression between the two groups was analyzed using the R package‘edge R’.Univariate,multivariate and Least Absolute Shrinkage and Selection Operator(LASSO)Cox regression analyses were performed to explore the prognostic value of TMErelated lncRNAs.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional analyses were also performed.The Connectivity Map(CMap)data set was used to screen molecular drugs that may treat UM.RESULTS:A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups.Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis.Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements.Among 269 differentially expressed lncRNAs,69 were up-regulated and 200 were down-regulated.Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age,TNM stage,tumor base diameter,and low and high risk indices had significant prognostic value.We screened the potential small-molecule drugs for UM,including W-13,AH-6809 and Imatinib.CONCLUSION:The prognostic markers identified in this study are reliable biomarkers of UM.This study expands our current understanding of the role of TME-related lncRNAs in UM genesis,which may lay the foundations for future treatment of this disease.

Effects of amniotic membrane transplantation on cytokines expression in chemically burned rat corneas

AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P =0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-gamma secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-beta secreted by Th2 cells were increased ( P <0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the nnRNA level in the AMT group, while the expression of EGF was significantly higher (P= 0.022) compared with the control. CONCLUSION: AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.

Side-stream smoking reduces intestinal inflammation and increases expression of tight junction proteins

AIM:To investigate the effect of side-stream smoking on gut microflora composition,intestinal inflammation and expression of tight junction proteins.METHODS:C57BL/6 mice were exposed to side-stream cigarette smoking for one hour daily over eight weeks.Cecal contents were collected for microbial composition analysis.Large intestine was collected for immunoblotting and quantitative reverse transcriptase polymerase chain reaction analyses of the inflammatory pathway and tight junction proteins.RESULTS:Side-stream smoking induced significant changes in the gut microbiota with increased mouse intestinal bacteria,Clostridium but decreased Fermicutes(Lactoccoci and Ruminococcus),Enterobacteriaceae family and Segmented filamentous baceteria compared to the control mice.Meanwhile,side-stream smoking inhibited the nuclear factor-κB pathway with reduced phosphorylation of p65 and IκBα,accompanied with unchanged mRNA expression of tumor necrosis factor-α or interleukin-6.The contents of tight junction proteins,claudin3 and ZO2 were up-regulated in the large intestine of mice exposed side-stream smoking.In addition,side-stream smoking increased c-Jun N-terminal kinase and p38 MAPK kinase signaling,while inhibiting AMPactivated protein kinase in the large intestine.CONCLUSION:Side-stream smoking altered gut microflora composition and reduced the inflammatory response,which was associated with increased expression of tight junction proteins.