Objective:The consensus molecular subtype (CMS) classification is based on the gene expression profiles, This article attempts to conduct a preliminary exploration and analysis of the clinical features of different CMS patients. We can give an individualized diagnosis and treatment for the patients.Methods:Seven GSE series of colorectal cancer gene expression profiles were downloaded by R software from the GEO database. A total of 1414 patients were included. Using the specific computational method published by Peter in 2017, the patients were divided into four groups: CMS1, CMS2, CMS3 and CMS4. The measurement data is expressed by Mean± SD, and the count data is expressed by n(%). The software of SPSS 18.0 was used to conduct analysis. Results:CMS1 tumors originated in the right colon (77.4%), while CMS2 mostly originated in the left colon (72.8%). The proportion of T 4 stage in CMS2 was 16.6%, while in the other three types was 23.3%, 29.3% and 24% respectively; the proportion of distant metastasis of CMS1 was the lowest (3.5%), while the distant metastasis rate of CMS4 was 18.2%. The KRAS mutation rates in CMS1 and CMS2 were 25.6% and 30.3% respectively, while in CMS3 it was up to 73.9%; the BRAF mutation rate in CMS1 was 45.5%, while the other three mutation rates were 0.6%, 6.2% and 5.9%, respectively; The average mutation rate of APC was 59.45%. Overall survival and progression-free survival analysis showed that the CMS4 interstitial type was the worst, while the CMS2 classic type had the best relative prognosis. Conclusions:CMS1 immunotype, the tumor has origin from right colon in female patients. MSI-H is often accompanied by BRAF gene mutation, this type patients has a refractory treatment response and poor prognosis. The classic CMS2 type is characterized by APC deletion mutation and Wnt activation, with good therapeutic effect and good prognosis. CMS3 metabolic type often harbor KRAS mutation, anti-EGFR treatment is not sensitive. Although this type is prone to relapse, but the chemotherapy is effective, so the overall survival prognosis is acceptable. CMS4 interstitial type with left colon tumor is prevalence. due to the activation of TGF-β and enhanced angiogenesis, this type tumor is prone to metastasis to distant site and has the worst prognosis.
Objective:To analyze how the surface marker of breast cancer stem cell related to chemotherapy resistance and postoperative recurrence.Methods:The GEO public database GSE25066 and GSE32603 were used to extract clinical data including pathological evaluation of neoadjuvant chemotherapy, postoperative follow-up recurrence and recurrence time, and the expression levels of the following 18 breast cancer stem cell marker genes were extracted: CD44, CD24, EPCAM, CD49f, PROM1, CD61, ALDH1A1, CD10, ALDH1A3, ABCG2, RANK, CD47, CD166, SLUG, SOX2, SXO9, SOX10, MYC. A total of 488 patients with GSE25066 were divided into pathology compete response(pCR) group ( n=99) and residual disease (RD) group ( n=389) according to the pathological analysis. Another 418 patients with complete recurrence data was divided into recurrence group ( n=111) and non-recurrence group ( n=307), they were used for prognosis analysis. The effects of each tumor stem cell marker on chemotherapy sensitivity and tumor recurrence were analyzed by logistic, lasso and COX regression. The gene expression level of GSE32603 before and after neoadjuvant chemotherapy were used to analyze the changes after neoadjuvant chemotherapy in 166 patients, to determine the enrichment effect of chemotherapy on stem cells. Results:In chemotherapy response analysis, tumor stem cell markers CD44( OR=0.78, 95% CI: 0.63-0.98) and SANI2 ( OR=0.80, 95% CI: 0.68-0.93) were negatively correlated with neoadjuvant chemotherapy sensitivity, and CD24( OR=1.18, 95% CI: 0.97-1.47) was positively correlated with chemosensitivity. In the recurrence correlation analysis, the patients with CD44 + ( OR=1.22, 95% CI: 0.98-1.51), CD24 low( OR=0.94, 95% CI: 0.79-1.11) and SANI2( OR=1.17, 95% CI: 1.00-1.37) expression have a high recurrence rate. As chemotherapy progressed, the MME, CD49f, SOX10, MYC, and SOX9 ( P<0.05) showed an enrichment process. Conclusions:Breast cancer stem cell markers CD44 + CD24 - and SLUG can be used to predict the efficacy of neoadjuvant chemotherapy and recurrence after tumor treatment. They are relatively stable marker for studying breast cancer stem cells.
Objective To investigate the effects of adenovirus vectors for BTB and cap'n'collar protein homology 1 (Bach1) small interfering RNA (siRNA) on antioxidanffactors and fibrosis related cytokines in lung fibroblasts (MLF) in transforming growth factor (TGF)-β1 induced mouse.Methods Bach1 siRNA recombinant adenovirus vectors and blankadenovirus vectorwere constructed,then the MLF cells were incubated with TGF-β1 (5 ng/ml) for 24 h and infected with blankvector and successful constructed Bach1 siRNAs.The messenger RNA (mRNA) and protein expression of Bach1,heme oxygenase (HO)-1,glutathione peroxidase 1 (GPx1) and nicotinamide-adenine dinucleotide phosphate:quinone oxidoreductase-1 (NQO1) in cell supernatants were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.Changes of fibrosis-related cytokines including TGF-β1 and interleukin (IL)-6 levels in cell supernatants were determined by enzyme-linked immunosorbent assay (ELISA).One-way analysis of variance (ANOVA) was performed for multiple group comparisons and LSD test was used to compare the two groups.Results Bach1 mRNA (2.127±0.089) and protein expression increased significantly after TGF-31 stimulation compared with blank group (1.000±0.067,t=-21.77,P<0.01),as well as the expression of fibrosis-related cytokines TGF-β1 (52±6) and IL-6 (34±6) in cell supernatants increased significantly after TGF-β1 stimulation compared with blank group (26±4,t=-11.11,P<0.01 and 20±5,t=-5.32,P<0.01),but the mRNA expression of HO-1 and GPx1 (0.403±0.040 and 0.567±0.112) also the protein expression decreased significantly compared with mRNA (1.000±0.181,t=25.57,P<0.01 and 1.000±0.212,t=6.68,P<0.05) and protein expression in blank group.Follow the Bach1 siRNA treatment,Bach1 mRNA (0.153±0.015) and protein levels were significantly downregulated compared with mRNA (2.129±0.089 and 1.973±0.035,F=1835.95,P<0.01) and protein expression of TGF-β1 and blank vector group,as well as TGF-β1 (26±3) and IL-6 (11±3) expression in cell supernatant were significantly inhibited compared with TGF-31 (52±6 and 34±6) and blankvector group (49±5 and 33±6) (F=22.25,P<0.01 and F=28.38,P<0.01).But the mRNA levels of HO-1 (3.303±0.294) and GPx1 (1.840±0.231) in MLF were promoted significantly compared with TGF-β1 (0.403±0.040 and 0.567±0.112) and blank vector group (0.353±0.057 and 0.667±0.090) (F=53.90,P<0.01 and F=526.25,P<0.01).Conclusion Silencing Bach1 rescues TGF-β1 induced reduction of antioxidants and increasethefibrosis in MLF cells.The study offers an experimental basis to explore pathogenesis of oxidative stress and antioxidant therapy for connective tissue disease related inter-stitial lung disease.
Objective To investigate the clinical and imaging features of patients with calcium pyrophosphate deposition (CPPD).Methods The clinical data and X-rays material of knee joint of 20 patients with CPPD were retrospectively analyzed.Pearson/Spearman's correlations analysis was used for statistical analysis with software version 15.0.Results The 20 patients with CPPD had demonstrated that the typical accumulation of calcium,which accounted for about 1.5%o(20/13 536) among patients over 55 years old who had knees X-ray at the same period in Chaoyang Hospital.Female patients of CPPD was 80% (16/20).Seventeen patients completed follow-up visits.The age of onset for CPPD ranged from 44 to 85 years old,the percentage of CPPD patients over 70 years old was 71%(12/17).Among the 17 cases of followed,14 cases (82%) were patients with paroxysmal arthritis with the initial site of knee joint (79%) and ankle joint (21%).Most patients suffered from moderate to severe pain,while some might have local congestion and increased skin temperature.Five patients had more than two different joints attacked by arthritis.The distribution of the affected areas was knee,ankle,hip,elbow,wrist and metacarpophalangeal joints.The median number of attack was 1.5 times a year,and the median duration of attack was 8.5 days.Among the 14 patients,Six cases of them had no recurrence after treatment,but six cases had recurrent attacks within a year.The imaging of lateral articular facet showed that calcium deposit was extended and thickness of calcification was increased.Plus osteophyte formation stage was 100% with an average of 3.0±1.6 and 85% sclerosis of articular facet.The rate of attacks of arthritis had a positive correlation with calcium deposition range of lateral articular facet (r=0.663,P=0.010) and a negative correlation with sclerosis of articular facet (r=-0.548,P=0.042).Conclusion Old patients with paroxysmal joint pain,patients with knee joint or other big joints as the initial joints involved,patients with long duration disease,patients who had more than two joints at attack and patients with calcium deposition in imaging,should be suspected for CPPD clinically.Moreover,patients with a wide range of calcium deposition are high likely to suffer from recurrent arthritis attack.
Objective By analyzing the clinical and radiographic manifestations of calcium pyrophosphate deposition disease (CPDD) to improve the recognization of the disease.Methods Clinical features,diagnosis and treatment of an old female patient with CPDD was reported with literature review.Results An old female patient presented with swollen and pain on the right knee without obvious causes eight years ago,which was characterized by slightly reddness of joint surface,warm of local skin.Thcn she gradually developed swollen and pain in left knee,right ankle,both wrists,bilateral meta-carpophalangeal (MCPJ) and right elbow joints with few joint symptoms and the joints swollen and pain could relieved spontaneouslyitself in about one week.X-ray showed the thin strip of cartilage calcifications in wrist triangular fibrocartilage disc,meniscus of knee and the pubic symphysis were parallel to the surface of cartilage.Examination of microscopy with refractive filter demonstrated that short rod crystals refraction in joint fluid.CPDD was diagnosed and treated with flushing of joint cavity and injections of betamethasone as well as nonsteroidal anti-inflammatory drug orally.Symptoms relieved after therapy.Conclusion Understanding the disease characteristics of CPDD is beneficial to for accurate diagnosis and treatment.
Objective Using continuous-wave near infrared spectroscopy (NIRS ),human cerebral tissue hemoglobin concentration index (tHI)is detected non-invasively and in real time,so that the change percentage of cerebral total hemoglobin concentration can be indicated and cerebral hemodynamics as well as oxygenation can be evaluated.Methods Based on the propagation of near-infrared light in human brain,the near-infrared oximeter was developed,and the cerebral tHI as well as cerebral oxygen saturation of 8 infants suffered from congenital heart disease were monitored non-invasively and in real time under cardiopulmonary bypass.Results During modified ultrapurification in the end of cardiopulmonary bypass,the cerebral tHI of all the infants increased significantly at the average speed of (0.0304 ±0.01 36)mM/(cm?min),P<0.001 . Comparing the end to the beginning of modified ultrapurification,the cerebral tHI increased for (18.8 ±7.5)%,because the hematocrit was increased by filtering out the redundant water in the blood.The cerebral oxygen <br> saturation increased for (5.3 ±4.1 )% (P <0.05 ), which was not so obvious as the increase trend of cerebral tHI.Conclusions During modified ultrapurification in the end of cardiopulmonary bypass,the changes of cerebral hemodynamics and oxygenation may be indicated effectively by cerebral tHI.
目的:比较两种血气管理方法,对中浅低温双瓣膜置换体外循环期间,大脑血流速度和氧代谢的影响.方法:选取连续24例中浅低温体外循环下行双瓣膜置换患者,使用CDI500进行连续血气监测.分别于以下5个时间点:麻醉诱导后(T1),体外循环转机10min时(T2),当鼻咽温降至25℃时,使用α稳态管理并校正血气15min后(T3),后改用pH稳态管理并校正血气15min后(T4),停机后10min(T5),使用经颅多普勒超声仪和近红外线光谱仪,测定大脑中动脉血流速度和脑氧饱和度,评估不同血气管理方法的脑保护效果.结果:与T1相比较,T2、T3脑血流速度和脑氧饱和度均有所减少,但差异无统计学意义(P>0.05).与T3相比较,T4时间点大脑血流速度和脑氧饱和度稍有升高,但差异并无统计学意义(P>0.05).结论:中浅低温体外循环期采用pH稳态血气管理并未明显增加大脑血流速度和氧供.
【目的】致病型问号钩端螺旋体(问号钩体, Leptospira interrogans)和腐生型双曲钩体(L. biflexa)能够大量合成菌体内贮藏物, 这可能是钩体在营养贫瘠环境中长时间存活的主要原因之一。本研究对钩体聚Beta羟基丁酸(PHB)贮藏物进行定性定量测定, 通过基因组分析补充定义PHB合成主要功能基因, 并采用分子生物学方法初步证明PHB合成途径的完整性, 为进一步研究PHB合成与钩体抗逆能力的关系奠定基础。【方法】采用脂类特异性尼罗红染色法和浓硫酸氧化-紫外分光光度计测定法, 对问号钩体和双曲钩体的PHB贮藏物进行定性定量测定; 采用生物信息学方法(BLAST和InterProscan/InterPro2Go), 通过同源性分析和功能结构域搜索寻找钩体基因组中的PHB合成相关基因; 最后采用克隆测序和定量RT-PCR技术检测相关基因表达情况, 初步验证生物信息学预测结果。【结果】尼罗红染色和氧化后比色定量实验证明钩体合成细菌常见贮藏物PHB, 问号钩体合成量为菌体干重的42%?45%, 双曲钩体合成量为64%?68%。尽管已公布的多个钩体基因组中均没有定义完整的PHB合成途径, 但本研究通过综合生物信息学分析, 在问号钩体和双曲钩体中鉴定了PHB合成途径的主要功能基因(phbC)。克隆测序和定量RT-PCR证实钩体转录表达大部分PHB合成相关基因(phbA/B/C), 说明钩体内该生物途径基本完整, 且部分高水平表达基因可能是钩体主要的PHB合成相关基因。【结论】问号钩体和双曲钩体均可合成PHB贮藏物, 且具有基本完整的PHB合成生物途径。
OBJECTIVETo separate and identify the surface proteins and secreted proteins of Toxoplasma gondii tachyzoites of RH strain.METHODST. gondii tachyzoites were cultured in Vero cells, and purified by filtration and Percoll cell separation solution. The biotin-labeled tachyzoites were lysed, and the surface and secreted proteins were separated by NeutrAvidin agarose beads. After condensation and SDS-PAGE, the protein were collected, digested and identified by LC/MS-MS.RESULTSA total of 785 T. gondii proteins were identified, 81 (10.3%) of which were originally annotated as the surface or secreted proteins. Among the highly-expressed (PSM>10) 65 proteins, 43 (66%) were originally annotated as surface or secreted proteins, while the others were predicted unknown proteins.CONCLUSIONThe surface and secreted proteins of T. gondii are separated by biotin labeling and avidin chromatography, among which some potential new surface or secreted proteins of T. gondii are identified.
Toxoplasmosis gondii is a common parasitic zoonoses worldwide.Construction of animal model is one of the most important ways to study it.To investigate the processes and outcomes after infection by using different animal models has provided a favorable experimental basis in preventing and curing toxoplasmosis which is far-reaching beneficial for human health.