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1.
Overcoming energy stress is a critical step for cells in solid tumors. Under this stress microenvironment, cancer cells significantly alter their energy metabolism to maintain cell survival and even metastasis. Our previous studies have shown that thioredoxin-1 (Trx-1) expression is increased in colorectal cancer (CRC) and promotes cell proliferation. However, the exact role and mechanism of how Trx-1 is involved in energy stress are still unknown. Here, we observed that glucose deprivation of CRC cells led to cell death and promoted the migration and invasion, accompanied by upregulation of Trx-1. Increased Trx-1 supported CRC cell survival under glucose deprivation. Whereas knockdown of Trx-1 sensitized CRC cells to glucose deprivation-induced cell death and reversed glucose deprivation-induced migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we identified glucose-6-phosphate dehydrogenase (G6PD) interacting with Trx-1 by HuPortTM human protein chip, co-IP and co-localization. Trx-1 promoted G6PD protein expression and activity under glucose deprivation, thereby increasing nicotinamide adenine dinucleotide phosphate (NADPH) generation. Moreover, G6PD knockdown sensitized CRC cells to glucose deprivation-induced cell death and suppressed glucose deprivation-induced migration, invasion, and EMT. Inhibition of Trx-1 and G6PD, together with inhibition of glycolysis using 2-deoxy-D-glucose (2DG), resulted in significant anti-tumor effects in CRC xenografts in vivo. These findings demonstrate a novel mechanism and may represent a new effective therapeutic regimen for CRC.  相似文献   

2.
目的 分析艰难梭菌感染与大肠癌及大肠腺瘤的相关性,为临床预防及治疗肠道肿瘤提供新思路。方法 收集2016年1月至2017年6月于甘肃省人民医院就诊的134例大肠癌患者、52例大肠腺瘤患者及100例健康对照者的粪便标本及临床资料,对粪便标本进行细胞毒性试验检测,分析大肠癌及大肠腺瘤与艰难梭菌感染的相关性。同时分析艰难梭菌感染与大肠癌临床特征及部分样本免疫组化(Her-2、P53、CDX2、CD56及Ki-67)结果的相关性。结果 (1)结直肠癌组检出13例艰难梭菌感染者(9.70%),大肠腺瘤组检出2例艰难梭菌感染者(3.85%),对照组未检出艰难梭菌感染者。结直肠癌组艰难梭菌感染率明显高于大肠腺瘤组及对照组(2=11.0953,P0.05)。(3)CDX2的表达与艰难梭菌感染具有相关性,CDX2阴性结直肠癌患者艰难梭菌感染率明显高于CDX2阳性患者(20.8% vs 2.8%,2=8.5224,P0.05)。结论 艰难梭菌感染与大肠癌的发生具有相关性,特别是与大肠癌病理分期及CDX2表达存在相关性。艰难梭菌感染与大肠腺瘤之间无显著相关性。  相似文献   

3.
目的 研究结直肠癌中的PTEN、p-ERK蛋白的表达及相互关系,初步探讨它们在结直肠癌的发生发展中的生物学意义.方法 应用免疫组织化学染色快捷法,检测40例结直肠癌组织、18例结直肠腺瘤、13例结直肠正常黏膜中PTEN蛋白、和p-ERK蛋白的表达情况,比较PTEN蛋白表达与临床病理指标的关系,及其与p-ERK蛋白表达的相关性.结果 1.结直肠癌癌组织PTEN蛋白表达的阳性率(57.5%)明显弱于腺瘤(72.2%)及正常组织(100%),组间比较差异有显著性(P<0.05),其表达水平与结直肠癌的分化程度、淋巴结转移、浸润深度、Dukes分期有关,与患者的性别、年龄,肿瘤大小及位置无关(P>0.05)2.结直肠癌组织p-ERK蛋白表达的阳性率(72.5%)明显高于正常结直肠黏膜组(0.00%)及腺瘤组(66.6%),组间比较差异有显著性(P<0.01),其表达随结直肠癌侵润深度增加、淋巴结转移、Duke分期的进展而增高.3.PTEN蛋白表达强度与p-ERK蛋白表达强度之间呈负相关(r=-0.452,P<0.05).结论 提示抑癌基因PTEN的表达与结直肠癌生物学行为密切相关;在结直肠癌发生、发展过程中,可能由于PTEN蛋白的低表达或失表达不能有效抑制ERK磷酸化,使细胞发生癌变,并促进癌变细胞的浸润、转移.  相似文献   

4.
This study examined whether neonatal paternal deprivation (PD: father was removed and pups were raised just by mother) or early deprivation (ED: pups were raised by both parents except separated from not only the dam but also the peers for three hours a day from PND 0 to 13) has long-term effects on anxiety and social behaviors of adult mandarin voles. Newborn mandarin voles of F2 generation were randomly assigned to one of three groups: bi-parental care (PC: pups were raised by both parents), PD and ED. The parental care behaviors of F1 generation were observed at the age of 0, 13 and 21 days (PND 0, 13, 21) of F2 generation of PC and PD groups. Moreover, each mandarin vole of F2 generation received an open field test and a social interaction test on PND 70 and PND 75, respectively. No significant differences of parental behavior were observed between mothers and fathers from PC families, showing typical parental behavior of socially monogamous rodents. In addition, no significant differences of maternal behaviors were found between mothers from PC and PD families, indicating no maternal compensation towards pups for the absence of the paternal care. In the open field test, mandarin voles from both PD and ED families displayed higher levels of anxiety and lower locomotor activity, relative to offspring of PC family. In the social interaction test, both PD and ED mandarin voles also showed lower levels of social behavior and higher levels of anxiety. Thus, both PD and ED significantly increase anxiety and reduce social behavior of adult mandarin voles, suggesting that variation in parental investment may lead to variation in anxiety and social behaviors in rodents with different mating systems.  相似文献   

5.
《Cancer epidemiology》2014,38(4):346-353
BackgroundThe gap in survival between older and younger European cancer patients is getting wider. It is possible that cancer in the elderly is being managed or treated differently than in their younger counterparts. This study aims to explore age disparities with respect to the clinical characteristics of the tumour, diagnostic pathway and treatment of colorectal cancer patients.MethodsWe conducted a multicenter cross sectional study in 5 Spanish regions. Consecutive incident cases of CRC were identified from pathology services. Measurements: From patient interviews, hospital and primary care clinical records, we collected data on symptoms, stage, doctors investigations, time duration to diagnosis/treatment, quality of care and treatment.Results777 symptomatic cases, 154 were older than 80 years. Stage was similar by age group. General symptoms were more frequent in the eldest and abdominal symptoms in the youngest. No differences were found regarding perception of symptom seriousness and symptom disclosure between age groups as no longer duration to diagnosis or treatment was observed in the oldest groups. In primary care, only ultrasound is more frequently ordered in those <65 years. Those >80 years had a significantly higher proportion of iron testing and abdominal XR requested in hospital. We observed a high resection rate independently of age but less adjuvant chemotherapy in Stage III colon cancer, and of radiotherapy in stage II and III rectal cancer as age increases.ConclusionThere are no relevant age disparities in the CRC diagnosis process with similar stage, duration to diagnosis, investigations and surgery. However, further improvements have to be made with respect to adjuvant therapy.  相似文献   

6.
Social deprivation is a severe stressor affecting a number of behavioral and physiological functions of gregarious species. It is assumed that, dependent upon the level of familiarity, social support given by a conspecific may attenuate the adverse consequences of stress. We investigated the effects of a 4 h maternal and littermate deprivation on behavioral reactions, stress hormone responses and brain corticosteroid receptor expression in 7-, 21- and 35-day-old domestic piglets (Sus scrofa) that were left alone or in the presence either of a familiar or unfamiliar age-matched piglet. Compared to control animals, all of the socially deprived piglets showed significant stress responses, such as impaired habituation in repeated open-field/novel-object tests, enhanced ACTH and cortisol release, and altered corticosteroid receptor expression in the hypothalamus. In addition, our results demonstrated that younger piglets had more difficulty coping with stress. The presence of an age-matched conspecific had a direct calming effect on the deprived piglet during the deprivation procedure, which was revealed by diminished stress-induced HPA activity and altered reactions in the behavioral test situations (e.g., activity, escape, and vocalization). Furthermore, because the presence of a familiar piglet causes a more pronounced buffering effect, we have shown for the first time that the degree of familiarity between the piglets may influence the effectiveness of social support. Our study emphasizes the benefits of social partners on positive welfare and the ability for pigs to cope with stress; therefore, our results should be taken into account during handling practices such as weaning and mixing.  相似文献   

7.

微生态失衡会影响宿主肠道黏液屏障功能,从而导致炎症性疾病和结直肠癌的发生。结肠上皮细胞通过分泌黏蛋白形成双层黏液层来保护自己免受恶劣环境和各种病原菌的侵袭。肠道菌群的组成能够影响黏蛋白的表达和肠道黏液屏障的功能,而饮食模式的变化又可以影响肠道菌群的组成。通过菌群疗法(包括粪菌移植)调节肠道菌群已成为改善微生态失调相关病理学表现的重要手段。因此,合理的饮食模式可以调节肠道菌群、细菌代谢物(后生元)与宿主之间的相互作用,并维持肠道黏液的组成和黏蛋白的合成,从而增强肠道黏液屏障的功能,降低肠道炎症性疾病和结直肠癌的风险。

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8.
Despite significant advances in the identification of specific genes and pathways important in the onset and progression of colorectal cancer (CRC), mechanistic insight into the relationship between driver and susceptibility genes is needed. In this paper, we systematically explore physical interactions between causative and putative CRC susceptibility genes to reveal the molecular mechanisms involved in tumor biology. In total, we identify 622 high-confidence protein–protein interactions between 42 CRC causative and 65 candidate susceptibility genes. Among the latter, 28 are located in the CRCS9 loci, related to the etiology of CRC, and 17 are co-expressed with well-established CRC drivers, which makes them excellent candidates for further functional studies. Moreover, we find a high degree of functional coherence between connected driver and susceptibility genes, which indicates that our network-based strategy is useful to gain insight into the underlying mechanisms of those proteins with unknown roles in CRC.  相似文献   

9.
The distribution of subcutaneous fat at the triceps and subscapular skinfold sites is described for four groups of children living in Guatemala. These groups are high socioeconomic status (SES) children of Ladino (mixed Spanish and Indian) ancestry, high SES children of European ancestry, low SES Ladino children, and very low SES Indian children. The method of Healy and Tanner (1981) is used, employing regression and principal components analysis of log transformed skinfold values to divide "fatness" into two uncorrelated variables: size (amount of fat) and shape (fat pattern). Significant differences exist between groups in size, with lower SES groups having less fat than higher SES groups. No significant difference in fat pattern exists between the high SES Ladino and high SES European children. Significant differences do exist between the high SES groups and the low SES groups. The relative amount of subscapular fat increases from the high SES Ladinos and high SES Europeans, to the low SES Ladinos, to the very low SES Indians. In the high SES European and high SES Ladino samples, girls have significantly more arm fat than boys. There is no significant difference in fat patterning between boys and girls in the two low SES samples. Finally, the relative amount of subscapular fat tends to increase with age in all four samples. These results indicate that fatness and fat patterning are independent anatomical characteristics, SES influences fat patterning; low SES children of both Ladino and Indian ancestry show greater reductions in arm fat than in trunk fat compared to high SES children, sexual dimorphism in fat patterning is SES dependent.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
Objective: To identity the relationship between indicators of self‐assessed symptom status, the reported impact of oral conditions and clinical indices, and the extent to which this relationship was moderated by gender and ethnicity. Design: Secondary analysis of data from an oral health survey of minority ethnic groups. Participants: Purposive sample of 376 individuals from minority ethnic groups in the United Kingdom recruited through community groups. Measures: Numbers of decayed, missing and filled teeth. Measures of self assessed symptoms, and impact upon quality of life. Results: Impact of oral conditions upon lifestyle was predicted by the number of missing teeth, the presence of pain on eating certain foods and the presence of toothache in the previous four weeks. Social variables (gender and ethnicity) did not predict impact cither singly or through interaction with symptoms. Conclusions: The findings support a linear model of the relationship between the experience of oro‐facial symptoms and impact on everyday life amongst older adults.  相似文献   

11.
目的:探讨VEGF(Vascular endothelial growth factor)在大肠癌中的表达及与肿瘤大小、病理分级、临床分期和预后的关系。方法:大肠癌组织蜡块50例、癌旁组织20例、正常组织20例。采用免疫组化S—P法对标本切片进行染色。结果:VEGF在癌组织中表达明显高于癌旁组织和正常组织,三者之间差异显著(P〈0.05)。VEGF抗原表达与病理分级、Dukes分期呈负相关性(P〈0.01)。结论:VEGF与大肠癌的发生有关,VEGF的检测可作为大肠癌预后评估的客观指标。  相似文献   

12.
潘林锋  张英杰  臧伟峰 《中国微生态学杂志》2021,33(11):1304-1307, 1312
目的探讨结直肠癌患者肠道菌群变化与炎症因子水平的相关性。方法选取2017年3月-2019年12月我院收治的结直肠癌患者60例为研究对象,另选我院同期健康体检者60例作为对照组,比较两组肠道菌群和炎性因子血清白细胞介素6(IL 6)、白细胞介素17(IL 17)、白细胞介素22(IL 22)和肿瘤坏死因子 α(TNF α)水平变化情况。采用Pearson检验分析肠道菌群和炎性因子水平的相关性。结果观察组双歧杆菌、乳酸杆菌和拟杆菌的菌落数相比对照组的菌落数明显降低,差异有统计学意义(P<0.05)。观察组具核梭杆菌、大肠杆菌和粪肠球菌菌落数明显高于对照组,差异有统计学意义(P<0.05)。炎性因子IL 6、IL 17、IL 22和TNF α水平在观察组较对照组明显升高,差异有统计学意义(P<0.05)。经Pearson相关性分析表明,双歧杆菌、乳酸杆菌和拟杆菌的菌落数与炎性因子IL 6、IL 17、IL 22和TNF α水平呈负相关(P<0.05),具核梭杆菌、大肠杆菌和粪肠球菌的菌落数与炎性因子IL 6、IL 17、IL 22和TNF α水平呈正相关(P<0.05)。结论结直肠癌患者肠道菌群失衡,并与炎性因子水平密切相关,肠道菌群失衡可能是促进病情发生发展的原因之一,可为治疗结直肠癌提供新的理论依据。  相似文献   

13.
BackgroundEvidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.MethodCox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women’s Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses.ResultsCompared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16–1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association.ConclusionOur data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.  相似文献   

14.
目的研究AEG-1在大肠癌组织和细胞中的表达,探讨AEG-1通过调控上皮间质转化和耐药参与大肠癌的进展。方法采用qRT-PCR检测AEG-1在大肠癌组织和细胞中的表达,统计AEG-1对大肠癌患者生存率的影响,分析其在不同癌症分期患者中的表达差异,并分析AEG-1表达量与大肠癌诊断敏感性的关系。采用体外实验将si-NC、pc-DNA-NC、si-AEG-1、pc-DNA-AEG-1转染到大肠癌SW116和LOVO细胞中,然后通过qRT-PCR检测转染效率以及AEG-1在两细胞系中的表达情况。采用CCK-8和克隆形成实验检测AEG-1对大肠癌细胞增殖的影响;采用流式细胞术检测转染后上皮间质转化和耐药情况的变化;采用Western blotting检测转染后上皮间质转化和耐药相关蛋白N-cadherin、E-cadherin、MRP的变化情况。结果 77例大肠癌患者组织中AEG-1表达水平明显高于对照组。浸润T3+T4期的患者中AEG-1的表达水平高于浸润T1+T2期患者。Ⅲ+Ⅳ期患者中AEG-1的表达水平高于Ⅰ+Ⅱ期。AEG-1高表达组患者OS时间明显低于低表达组。AEG-1表达量与大肠癌诊断敏感性之间呈显著正相关。在LOVO细胞系中,降低AEG-1表达后其细胞活力、侵袭力明显降低,同时间质细胞标志蛋白N-cadherin、上皮细胞标志蛋白E-cadherin、多药耐药相关蛋白MRP表达量降低。在SW116细胞系中,过表达AEG-1后上皮间质转化、耐药相关蛋白表达量显著升高。结论 AEG-1在大肠癌组织和细胞中的表达量明显上升,AEG-1通过调控上皮间质转化和耐药参与大肠癌的发生发展,为大肠癌的治疗提供了新的理论依据和新的靶点。  相似文献   

15.
Proteomic analysis of human tissue and plasma samples has been a useful tool in recent years for the identification of potential biomarkers to aid in the early diagnosis of colorectal cancer. However, biomarkers relating to the crucial transition between adenomatous lesions and invasive colorectal malignancy have not previously been described. The work of Choi et al. (Proteomics 2013, 13, 2361–2374) attempts to address this issue. Using plasma samples from age‐matched patients with colorectal adenomas or invasive disease this group identified a range of plasma proteins and cytokines that were differentially expressed. This information not only provides insights into the biology of the adenoma to carcinoma progression sequence but it also represents a step towards the goal of achieving diagnostically accurate and clinically acceptable biomarkers in early colorectal cancer.  相似文献   

16.
BackgroundSocial networking sites are widely used by university students. This study investigated the purposes for which social networking sites are used and their effects on learning, social interaction, and sleep duration.Material and methodsA cross-sectional study was conducted among 300, 17–29-year-old female students at Prince Sattam bin Abdul Aziz University. A questionnaire was used to collect data. Chi-squared (Fisher’s exact test) test was used to analyze the data.ResultsThe results showed that 97% of the students used social media applications. Only 1% of them used social media for academic purposes. Whereas 35% of them used these platforms to chat with others, 43% of them browsed these sites to pass time. Moreover, 57% of them were addicted to social media. Additionally, 52% of them reported that social media use had affected their learning activities, 66% of them felt more drawn toward social media than toward academic activities, and 74% of them spent their free time on social media platforms. The most popular applications (i.e., based on usage) were Snapchat (45%), Instagram (22%), Twitter (18%), and WhatsApp (7%). Further, 46% and 39% of them reported going to bed between 11 pm and 12 am and between 1 am and 2 am, respectively. Finally, 68% of them attributed their delayed bedtime to social media use, and 59% of them reported that social media had affected their social interactions.ConclusionsA majority of the participants reported prolonged use of social networking sites for nonacademic purposes. These habitual behaviors can distract students from their academic work, adversely affect their academic performance, social interactions, and sleep duration, and lead to a sedentary lifestyle and physical inactivity, which in turn can render them vulnerable to non-communicable diseases and mental health problems.  相似文献   

17.
Herlyn  D.  Somasundaram  R.  Zaloudik  J.  Jacob  L.  Harris  D.  Kieny  M. -P.  Sears  H.  Mastrangelo  M. 《Cell biochemistry and biophysics》1994,24(1-3):143-153
The CO17-1A/GA733 antigen (Ag), bound by monoclonal antibodies (MAb) CO17-1A and GA733 that define two different epitopes on the Ag, has proven a useful target in passive and active immunotherapy of colorectal carcinoma (CRC). Previous studies suggest that the antitumor effects demonstrated in MAb-treated patients may be mediated by idiotypic cascades. In approaches to active immunotherapy against the Ag, polyclonal goat and monoclonal rat anti-idiotypic antibodies (Ab2) directed against MAb CO17-1A or GA733 (Ab1) were administered as alum precipitates to 54 patients with CRC (stage Dukes' B, C, and D). The majority of the patients treated with the various Ab2 preparations developed anti-anti-idiotypic antibodies (Ab3) that specifically bound to the CO17-1A or GA733 epitope and shared idiotopes with the corresponding Ab1. Approximately 30% of the patients tested developed specific cellular immunity, i.e., Ag-specific T-cells mediating delayed-type hypersensitivity (DTH) reaction in vivo or proliferating on stimulation with the Ag in vitro. The humoral and cellular immune responses may underlie the clinical responses observed in some of the treated patients. Recently, the CO17-1A/GA733 Ag has been molecularly cloned and expressed in baculo-, adeno-, and vaccinia viruses. In preclinical studies, these recombinant Ag preparations elicited specific humoral immunity (cytotoxic antibodies) and cellular immunity (DTH-reactive and proliferative T-cells), similar to the native Ag. Antibody titers elicited in experimental animals by recombinant Ag were significantly higher than those elicited by Ab2, presumably because Ag expresses numerous epitopes, whereas Ab2 mimics a single epitope. Recombinant CO17-1A/GA733 Ag has potential as a vaccine for CRC patients.  相似文献   

18.
目的 探究二甲双胍抑制肠癌的生长及调控肠道菌群的作用。 方法 20只C57BL/6J小鼠通过AOM DSS诱导结直肠癌发生,分成2组每天分别灌胃生理盐水及二甲双胍溶液,12周后处死小鼠,收集结直肠组织及粪便,比较2组小鼠肠道肿瘤个数及大小并进行H&E染色分析,运用16S rRNA基因测序技术检测小鼠肠道菌群组成,使用QIIME软件分析菌群物种分类、物种多样性指数及组间显著性差异。 结果 2组小鼠体质量随周龄增加均呈现增长趋势,且实验结束时体质量差异无统计学意义(t=0.743 1,P=0.469 7)。与对照组相比,接受二甲双胍灌胃的实验组小鼠结直肠肿瘤数量减少(t=2.260 0,P=0.040 3)且尺寸偏小(t=2.570 0,P=0.014 4)。粪便菌群测序结果显示实验组小鼠肠道菌群丰富度增加(P0.05)。在属水平上,实验组Akkermansia、Ruminococcus及Clostridium Ⅹa和Ⅳ等细菌的丰富度增加。 结论 二甲双胍能够调控肠道菌群的组成,增加肠道内产SCFAs细菌的定植,并抑制肠癌的发生发展。  相似文献   

19.
The question of whether attributes of the combs of laying hens have any consistent relationship with dominance behaviour has yet to be answered unequivocally. This study sought to address this by investigating whether a relationship existed between the competitive ability of hens within stable groups and the size or colour of their combs. Pullets (n = 120, Hy-line® Variety Brown) were allocated randomly to eight groups of 15 hens for 32 weeks. Over this period the length and height of each hen's comb was measured regularly to estimate the total comb area and hens were weighed. In weeks 3-10 the aggressive interactions between hens in each group were observed to calculate a behavioural dominance score (David's score) for each hen. This score was based on the outcome of agonistic interactions with other group members; and accounts for the relative strengths of all opponents. Thus dominance scores reflected the competitive ability of hens from their overall within-group fighting success. The luminance, purity and dominant wavelength of the colour of each hen's comb was measured in week 27 using a telespectroradiometer. Hens with higher dominance scores had larger combs than those with lower dominance scores (gradient of slope = 0.008 ± 0.002, P < 0.001); this relationship was consistent across the experiment. There was no association between body weight and dominance score but there was a significant inverse relationship between dominance score and the dominant wavelength of the comb (gradient of slope = −0.067 ± 0.023, P < 0.01). This indicated that hens with combs perceived by humans as more yellow-red than pure red were generally more successful competitors. Further research is required to ascertain whether or not hens utilise this information on comb size and the underexplored area of comb colour to assess the competitive ability of their opponents.  相似文献   

20.
肠道微生物群是人体内环境的重要组成部分,与宿主共进化、共代谢、共发育,并与宿主之间相互调控,影响宿主健康。近年研究显示,肠道微生物群参与了结直肠癌的发生和发展。了解肠道微生物群的特征性变化及其诱发结直肠癌的机制对于结直肠癌的防治有着重要意义。目前以肠道微生物群为靶点的干预性基础研究也取得了一些突破性的研究进展。本文主要对结直肠癌患者肠道微生物群的变化、其可能的致病机制及临床相关研究进展等进行综述。  相似文献   

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