Introduction: Obesity is a major risk factor for metabolic and cardiovascular disorders. Recently, emerging biomarkers, such as the Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP), have garnered attention for their utility in assessing visceral obesity. Bilirubin, a potent endogenous antioxidant, has been associated with protective effects against various diseases. This study aims to investigate the relationship between serum total bilirubin (STB) levels and VAI/LAP in adults. Methods: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2003 and 2020. The calculation of VAI and LAP was performed computationally. Weighted multivariate regression models were used to explore the potential correlation between STB levels and VAI or LAP. RCS curves were used to identify the potential non-linear relationship. Moreover, subgroup analyses were conducted to examine heterogeneity across different populations. Results: The analysis included a cohort of 10,625 individuals aged 20 to 85 years. Both unadjusted and adjusted statistical models revealed a significant negative association between STB levels and VAI or LAP (all P< 0.001). RCS indicates that these relationships are linear. Subgroup analyses identified particularly strong associations in non-smokers aged 20-59 without hypertension/diabetes (P < 0.05). Discussion: Our study's strengths include the use of nationally representative data with appropriate weighting, comprehensive adjustment for confounding variables, and pioneering research on the link between serum bilirubin levels and visceral fat indices, which may indicate early metabolic risk markers. This finding highlights the significant role of bilirubin in body fat distribution and lipid metabolism. Conclusion: This study revealed that STB was associated with VAI or LAP among the specific general American population aged 20-59 without hypertension/diabetes. Further prospective investigations are warranted to clarify the temporal relationship between STB and novel obesity indices.

Absorption plays a pivotal role in the development of nutritional obesity. However, little is known about nutritional-obesity–related absorption augmentation. The aim of this study was to observe the morphological features of villous absorption in fasting–refeeding (FaF) and nutritional obesity. After 48 h of fasting, adult male Sprague Dawley (SD) rats were refed, and their intestines were sampled 2–6 h after feeding. After 20 weeks of modeling, we collected the intestines of obese rats. Samples were processed and observed under a light microscope and an electron microscope. Villous-tip openings and the subepithelial space formed an unrestricted-absorption channel connecting the enteric lumen with the submucosal lymphatic sinus and porous capillaries. FaF and high ingestion of a high-fat diet (HFD) were effective inducing factors. Channel absorption of villi was related to apoptosis and the loss of tight junctions in the epithelium. In cases of FaF or obesity, villous-tip openings and the subepithelial space of the villi formed a continuous channel, providing transient and functional unrestricted channel absorption.

To compare the differences in floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats fed in a conventional or specific-pathogen free (SPF) environment and rats fed a high-fat diet (HFD), and the V3–V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was then amplified and sequenced. Compared with feces, about 60% of the bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units (OTUs) < 1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). The dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater β-diversity, and the distance between in-group samples was nearer than that between paired ileum–feces samples. Moreover, the ileum shared various biomarkers and functions with feces (p < 0.05). The HFD and SPF conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or β-diversity of samples. The present findings suggested that, under conventional circumstances, fecal bacteria can represent approximately 40% of the low abundant ileal bacterial genera and that dominant fecal bacteria failed to represent the ileal dominant flora. Moreover, fecal flora diversity does not reflect β-diversity in the ileum.

The cell is the basic unit of life. It is composed of organelles and various organic and inorganic biomolecules. Recent 16S ribosomal ribonucleic acid (16S rRNA) gene sequencing studies have revealed the presence of tissue bacteria in both tumor and normal tissues. Recently, we found that the liver microbiome resided in hepatocytes. Here, we further report on the cellular microbiome in the parenchymal cells of visceral organs as inherent inhabitants. We performed 16S rRNA gene sequencing on visceral organs of male adult Sprague Dawley (SD) rats, pregnant rats, newborn rats, and fetuses and placentas; then, we performed fluorescence in situ hybridization and immunofluorescence in visceral organs. Furthermore, we performed Western blotting on nuclear and cytoplasmic extractions of visceral organs of SD rats and cell lines HepG2, Huh-7, Hepa1-6, and HSC-T6. A high abundance of 16S rRNA gene was detected in the visceral organs of male adult, pregnant, newborn, and fetal rats as well as their placentas. The number of operational taxonomic units (OTUs) of visceral bacteria was higher than that of the feces and ileum bacteria. Bacterial 16S rRNA, lipopolysaccharide (LPS), and lipoteichoic acid (LTA) were found in the parenchymal cells of visceral organs, as well as in HepG2, Huh-7, HSC-T6, and Hepa1-6 cells. LPS consistently appeared in the nucleus of cells, while LTA was mainly found in the cytoplasm. In conclusion, the cellular microbiome is an intrinsic component of cells. Gram-negative bacteria are located in the nucleus, and Gram-positive bacteria are located in the cytoplasm. This differs from the gut microbiome and may be inherited.

The tumor and tissue microbiota of human beings have recently been investigated. Gut permeability is known as a possible resource for the positive detection of tissue bacteria. Herein, we report that microbiota were detected in high abundance in the hepatocytes of healthy rats and that they were shared with the gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After the rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50±6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67±70.14, 729–893). Rats showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of the genomes of annotated bacteria was correlated with metabolism (79.92±0.24%). Gram negativity was about 1.6 times higher than gram positivity. The liver microbiome was shared with both the small and large intestines but showed significantly higher richness and evenness than the gut microbiome, and the β-diversity results showed that the liver microbiome exhibited significantly higher similarity than the small and large intestines (P<0.05). Our results suggest that the bacteria in the liver microbiome are hidden intracellular inhabitants in healthy rat livers.

非酒精性脂肪性肝病(NAFLD)是以肝细胞内脂质过度沉积为主要特征的一系列肝脏异常病变,也是全球范围内最常见的慢性肝病.自噬是细胞降解自身成分、参与维持器官功能及机体稳态的一种基本细胞过程,与NAFLD的进展存在密切联系.机体遭受的高脂、缺氧和压力等在肝脏内形成了细胞外微环境的异常改变,这些异常微环境可能通过诱导的肝脏细胞自噬促进NAFLD的发生发展.本文基于肝脏内的多种微环境特征,对肝细胞、Kupffer细胞、肝星状细胞等肝脏细胞的自噬在NAFLD进展中的作用和机制进行综述.

非酒精性脂肪性肝病(NAFLD)是目前最为常见的慢性肝病,并与多种代谢性疾病密切相关,如2型糖尿病、胰岛素抵抗,以及与高血压和血脂异常相关的心脑血管并发症.NAFLD病因和病理机制复杂,微环境因素和基因表达调节异常存在于疾病进展的各个阶段,并通过累加效应促进疾病发展.缺氧诱导因子(HIF)是核转录因子、Yes相关蛋白(YAP)是转录辅助调节因子,二者通过调节肝脂质沉积与氧化应激,促进炎性因子释放,与NAFLD进展密切相关.本文对HIF-1α/YAP在NAFLD及其相关代谢性疾病进展中的作用进行综述,为探索NAFLD疾病进展过程中的相关治疗靶点提供理论依据.

对大肠杆菌和金黄色葡萄球菌进行正己酸的抗性试验,以研究正己酸对病原菌的抑制作用.试验采用等浓度梯度稀释、光密度值测定、平板涂布方法、牛津杯法,分别测定大肠杆菌及金黄色葡萄球菌的的最小抑菌浓度(minimum inhibitory concentration,MIC)以及最小杀菌浓度(mini-mum bactericidal concentration,MBC),绘制1/2MIC以及MIC处理过的大肠杆菌以及金黄色葡萄球菌的生长曲线,抑菌圈直径,结合扫描电镜图片分析最小杀菌浓度处理后的细胞形态结构的变化.结果表明:正己酸对大肠杆菌的最小抑菌浓度为700μg/mL、对金黄色葡萄球菌的最小抑菌浓度为1000μg/mL;对大肠杆菌的最小杀菌浓度为1000μg/mL、对金黄色葡萄球菌的最小杀菌浓度为1300μg/mL;当正己酸浓度为1600μg/mL时,电镜下,大肠杆菌数量较少,金黄色葡萄球菌数量少且呈现出细胞破裂萎缩现象.综上,正己酸对大肠杆菌和金黄葡萄球菌有抑制作用,破坏了金黄葡萄球菌的细胞膜结构.

脑源性神经营养因子(BDNF)是一种调节能量平衡的新兴介质,参与能量代谢的多种生理和病理过程.能量代谢失衡是肥胖的主要特征.本研究主要论述BDNF在能量代谢调节及肥胖中的相关分子机制、信号通路,发现其既可以通过中枢神经元直接作用于下丘脑,也可对外周的靶器官发挥作用;异常表达的BDNF通过受体原肌球蛋白受体激酶B/p75神经营养因子受体或转录共激活因子Yes相关蛋白/PDZ结合基序蛋白等效应蛋白共同作用,调节细胞内经典的增殖、分化和凋亡等,参与脂肪调节导致肥胖.

Abstract Background: The occurrence of serious diseases, such as inflammatory diseases and cancer, in the small intestine is significantly lower than that in the colon. The differentiation of small-intestine microbiota from large-intestine microbiota might hold great significance. To compare floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats, and the V3–V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was amplified and sequenced. We subjected the data to bioinformatics analyzing.Results: Compared with feces, about 50% of bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units [OTUs] <1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). Dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater β-diversity, and the distance between in-group samples was nearer than that between paired ileum–feces samples. Moreover, the ileum shared various biomarkers and functions with feces (P < 0.05). A high-fat diet (HFD) and specific-pathogen–free (SPF) conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or β-diversity of samples. Intestinal microbiota were composed of high-prevalence dominant, low-prevalence dominant, and less-dominant bacteria.Conclusions: The present findings suggested that ileal and fecal bacteria were different structurally and functionally. These differences might be key to the fundamental protection of the small intestine from diseases.

Abstract Aim The cell is the basic unit of life. It is composed of organelles and various organic and inorganic biomolecules. Recent 16S rRNA gene sequencing studies have revealed the existence of tissue microbiota, in both tumor tissues and normal tissues. Recently, we found that liver microbiota resided in hepatocytes. Here, we further report on cellular microbiota in parenchymal cells of visceral organs as inherent inhabitants. Methods The 16S rRNA gene sequencing was performed on visceral organs of male adult Sprague-Dawley (SD) rats (n = 6), pregnant rats (n = 6), newborn rats (n = 6, from the same litter), and fetuses and placentas (n = 6). Fluorescence in situ hybridization and immunofluorescence were performed in situ in visceral organs of male adult SD rats. Western blotting was performed on nuclear and cytoplasmic extractions of visceral organs of SD rats and cell lines HepG2, Huh-7, Hepa1-6, and HSC-T6. Results (1) A high abundance of 16S rRNA gene were detected in the visceral organs of male adult, pregnant, newborn, and fetal rats as well as their placentas. (2) In male adult rats, (i) the number of operational taxonomic units (OTUs) of visceral bacteria (1432.00 ± 39.87) was higher than that of the feces and ileum bacteria (1009.00 ± 5.66), P < 0.05. Nearly all the OTUs were shared across the organs and intestinal contents but the dominant bacteria varied. The alpha diversity of the visceral microbiota was significantly higher than that of the intestinal microbiota, P < 0.05. The similarity of visceral bacteria was significantly higher than that of the visceral organs to the intestine or the distance between intestinal microbiota, P < 0.05. (ii) Among 613 annotated genera visceral bacteria, 404 types of bacteria were shared across organs, including the top 10 abundant bacteria. Other bacteria were shared between a subset of organs, and very few bacteria were exclusive to only one organ. In an individual, about 15–40% (23.23% ± 7.91%) of visceral bacteria were shared and 8–11% (9.56% ± 1.37%) were exclusive to a specific organ. In each type of organ, the abundance of dominant bacteria varied among individuals. Each organ had exclusive bacteria with a low abundance (from 1 to 672). (iii) According to a KEGG analysis, the functional composition of visceral bacteria genomes were the same but differed from that of gut bacteria. (3) Bacterial 16S rRNA, LPS, and LTA were found in the parenchymal cells of visceral organs and in HepG2, Huh-7, HSC-T6, and Hepa1-6 cells. LPS consistently appeared in the nucleus of cells, while LTA was mainly found in the cytoplasm. (4) The visceral bacteria of newborn rats were shared with bacteria of skin tissue and maternal milk clots. The species richness of skin tissue and milk clots were the same, but were higher than that of intestinal tissues (including the contents), visceral organs, and skeletal muscle, P < 0.05. The species evenness of skin tissue was higher than that of the visceral organs and skeletal muscle. (5) The fetuses and placentas showed nearly the same species richness and evenness as the visceral organs of pregnant rats, but the distribution in the fetuses and placentas differed. Conclusions Cellular microbiota are the intrinsic components of cells. Gram-negative bacteria are located in the nucleus, and gram-positive bacteria are located in the cytoplasm. This differs from the gut microbiota and may be inherited.

肝纤维化是大多数慢性肝病进展为肝硬化的共同病理改变,是肝脏的一种损伤修复反应.目前与纤维化有关的慢性肝病严重影响着人类身体健康.肝损伤修复反应导致肝星状细胞(hepatic stellate cells,HSCs)活化,从而引起细胞外基质(extracellular matrix,ECM)的过度沉积,是形成肝纤维化的主要驱动因素.Rho三磷酸鸟苷酶(Rho GTPases)是一类调控真核细胞内信号转导通路的重要分子开关,通过激活下游Rho相关卷曲螺旋形成蛋白激酶(Rho associated coiled coil forming protein kinase,ROCK)参与调控细胞的收缩、黏附迁移、生长分裂、脂质代谢、转录调控、凋亡等多种生物学行为与功能.Rho/ROCK信号通路与HSCs的各种反应密切相关,其激活可以促进HSCs活化.本文就Rho/ROCK信号通路对HSCs活化的影响作一综述,揭示该信号通路在HSCs活化中的重要作用,为抗纤维化的治疗提供一些新思路.

Rapid and accurate detection can help optimize patient treatment and improve infection control against nosocomial carbapenemase-producing organisms (CPO). In this study, a total of 217 routine clinical isolates (Enterobacterales and A. baumannii), including 178 CPOs and 39 non-CPOs, were tested to evaluate the performance of six phenotypic carbapenemase detection and classification assays, i.e., BD Phoenix CPO detect panel, Rapidec Carba-NP, O.K.N detection kit, and three carbapenem inactivation methods (CIMs; mCIM, eCIM, sCIM). The overall detection sensitivity and specificity were 98.78% (95.21–99.79%) and 79.49% (63.06–90.13%), respectively, for the BD phoenix CPO P/N test; 91.93% (86.30–95.45%) and 100% (88.83–100%), respectively, for the Rapidec Carba-NP; 98.06% (94.00–99.50%) and 97.44% (84.92–99.87%), respectively, for mCIM; and 96.89% (92.52–98.85%) and 94.87% (81.37–99.11%), respectively, for sCIM. The classification sensitivity and specificity for the BD phoenix CPO Ambler test, the O.K.N detection kit, and the mCIM and eCIM were 56.71% (48.75–64.34%) and 94.87% (81.37–99.11%), 99.28% (95.43–99.96%) and 100% (88.83–100%), and 92.90% (87.35–96.23%) and 97.44% (84.92–99.87%), respectively. All detection assays were reliable in detecting carbapenemase. However, the Rapidec Carba-NP and mCIM were insufficient in detecting OXA-48-like enzymes. The BD phoenix CPO detect panel had a strong ability to detect carbapenemase but failed to classify 48/59 (81.36%) KPC, 8/52 (15.38%) NDM, 8/22 (36.36%) OXA-23-like, and 6/11 (54.55%) dual enzymes. The O.K.N detection kit accurately detected and differentiated KPC, NDM, and OXA-48-like enzymes existing alone or in combination. The results of this study will support reliable laboratory work tools and promote therapeutic and infection control decisions.

目的 肠道菌群与营养性肥胖关系密切,但多数研究集中在大肠粪菌,小肠作为吸收的主要场所,其菌群还缺乏研究,本文通过微生物多样性分析,探索回肠与结肠菌群差异及营养性肥胖相关菌群.方法 混合喂养法建立营养性肥胖SD大鼠模型,chow继续喂养60 d消除HFD的影响,提取回肠、结肠内容物总DNA,PCR扩增16S rRNA基因V3+V4区并测序,建立OTUs,通过Silva数据库进行注释和分类学分析.结果 (1)alpha分析显示回肠菌群数量高于结肠(chao1、ace),而多样性低于结肠(simpson、shannon)(P<0.05);(2)beta分析显示回肠与结肠以及回肠样本间物种相似度较低;(3)OTUs注释及聚类分析显示回肠与结肠优势菌(丰度排名top 10)的类型和丰度分布重叠性较低(属水平);(4)HFD-OR大鼠回肠Rothia丰度增加,而Romboutsia丰度降低.结论 回肠与结肠具有不同的菌群多样性;Rothia菌和Romboutsia菌可能是参与肥胖发生的关键回肠菌群.

通过为期三月的教学观摩,对美国UCLA本科生阶段、医学院阶段、博士生阶段的医学教育理念及教学设计进行分析.美国的医学教育具有很扎实的前期基础,医学生的专业教育专注于培养学生自主学习的能力,使学生尽早进入临床角色.师资团队主要来自于一线的临床医生,结合临床实际,开展从基础到临床的系统性教学.PhD教学以专题的形式进行,Lecture结合文献阅读,使研究生很快进入科研实践中.这些特征对我国医学教育的现代化改革具有较大的指导意义.

Objective This study aimed to determine the risk factors for intra-abdominal infections (IAIs), assess the clinical outcomes of IAIs, and investigate the spectrum and antimicrobial resistance of major pathogens causing IAIs. Patients and methods This prospective observational study enrolled patients from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections (CARES) program between 2007 and 2016. Data on the clinicopathological factors and causative pathogens were collected. The results of antimicrobial susceptibility tests were interpreted according to the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2017. Results A total of 2,756 patients were included. The 30-day all-cause mortality was 9.5% (262/2,756). Multivariable analysis showed that the following independent risk factors were associated with the 30-day mortality: age >60 years, pulmonary disease, tracheal cannula, infection occurring in intensive care unit (ICU), prior admission within 3 months, antibiotic use before infection, recent use of immunosuppressants, and multidrug-resistant organisms. In addition, 2,913 clinical isolates were collected. The Gram-negative and Gram-positive bacteria accounted for 70.8% and 29.2% of all isolates, respectively. The most common pathogens were Escherichia coli (33.4%), Klebsiella pneumoniae (10.8%), and Enterococcus faecium (10.7%). Pseudomonas aeruginosa and Acinetobacter baumannii were the most common non-Enterobacteriaceae Gram-negative pathogens. E. faecium, Enterococcus faecalis, and Staphylococcus aureus were the most common Gram-positive pathogens. E. coli, A. baumannii, and Enterobacter cloacae were more commonly found in ICU patients than in non-ICU patients. Overall, the antibiotics tested in the CARES exhibited diminished susceptibility to pathogens over the study period, especially extended spectrum β-lactamase producing isolates. Conclusion Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of IAIs and their susceptibility to antibiotics through the CARES is warranted.

本文讨论了肝星状细胞活化与肝纤维化之间的关系,阐述了肝星状细胞活化相关因素和非酒精性脂肪肝病的相关病理变化以及它们对肝纤维化的影响.通过总结国内外对肝纤维化和肝星状细胞活化的研究方法和所取得的成就,探究肝星状细胞活化及其在高脂膳食性非酒精性脂肪肝致使肝纤维化中的作用.

Objective To investigate the effects of 12C6+ heavy ion irradiation on migration,invasion and adhesion of human hepatocellular carcinoma HepG2 cells and its related mechanisms.Methods The logarithmic HepG2 cells were irradiated by 0,1,2,4 Gy of 12C6+ heavy ion ray and then the migration and invasion were determined by Transwell method,the adhesion ability was detected by MTS method (inner salt method),and the matrix metalloproteinases-2 (MMP-2) and MMP-9 protein expression was detected by Western blot.Results After 12C6+ heavy ion rays irradiation,compared with the 0 Gy group,with the increase of radiation dose,HepG2 cell migration ability decreased significantly,the invasion ability also decreased (P ＜ 0.05);HepG2 cell adhesion ability enhanced (P ＜ 0.05);the amount of MMP-2 and MMP-9 expression in HepG2 cells were down-regulated (P ＜ 0.05).Conclusion 12C6+ heavy ion irradiation can enhance the adhesion ability and inhibit the migration and invasion ability of HepG2 cells,which may be related to the down-regulation of MMP-2 and MMP-9 expression.

Ethnopharmacological relevance: Anoectochilus roxburghii has been used as a health food and a herb for treatment diabetes in China for hundreds years. Anoectochilus roxburghii polysaccharose (ARP) is the major active component of the plant.Aim of the study: The present study investigated the vascular protection of ARP in vivo and in vitro experiments.Materials and methods: Hypoglycemic activity of ARP was examined in diabetic mice. Moreover, the further vascular protective effects in vitro were investigated in human umbilical vein endothelial cells (HUVECs) stimulated by high glucose (HG, 35 mM).Results: Compared with untreated diabetic mice, ARP (100 or 300 mg/kg) caused a significant decrease in blood glucose levels. Histological examination showed that ARP ameliorated endothelial damage to some extent, especially ARP at dosage of 300 mg/kg. In vitro assay, pretreatment with ARP (10, 20 and 30 mu g/mL) markedly inhibited generations of reactive oxygen species (ROS), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) in HG-induced HUVECs. ARP pretreatment not only suppressed HG-induced matrix metalloproteinases (MMPs) activity via increasing the expression of the tissue inhibitors of MMPs (TIMPs), but also adjusted the MMPs/TIMPs balance to maintain homeostasis of vascular structure. Moreover, pretreatment with ARP could significantly reduce p-NF-kappa B p65, p-p38 MAPK expression levels in HG-induced HUVECs.Conclusions: The vascular protective effects of ARP might be associated with NF-kappa B and p38 MAPK pathway. ARP might be used as useful substance in the treatment of vasculopathy in diabetic patients.

All tumors, both benign and metastatic, undergo an avascular growth stage with nutrients supplied by the surrounding tissue. This avascular growth process is much easier to carry out in more qualitative and quantitative experiments starting from tumor spheroids in vitro with reliable reproducibility. Essentially, this tumor progression would be described as a sequence of phenotypes. Using agent-based simulation in a two-dimensional spatial lattice, we constructed a composite growth model in which the phenotypic behavior of tumor cells depends on not only the local nutrient concentration and cell count but also the game among cells. Our simulation results demonstrated that in silico tumors are qualitatively similar to those observed in tumor spheroid experiments. We also found that the payoffs in the game between two living cell phenotypes can influence the growth velocity and surface roughness of tumors at the same time. Finally, this current model is flexible and can be easily extended to discuss other situations, such as environmental heterogeneity and mutation.