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Objective:To investigate the relationship between transcription factors (TFs) and the prognosis of colon cancer, and to construct a prognosis model through TCGA and GEO dual databases, so as to quantify the risk of patients and guide clinical treatment decisions.Methods:The transcriptome and clinical data of colon cancer in TCGA and GEO databases were used in this study. The transcriptome data were annotated and the gene expression was calculated. The difference analysis of TFs in TCGA and GEO (log2FC > 1, P-value (Fdr) < 0.05) was performed. The difference TFs of double data intersection were used for correlation prognosis analysis ( P<0.01). The risk coefficient and risk value of prognosis-related TFs were calculated by COX multivariate analysis, and the prognosis model of TFs was constructed by COX model with "survival" and "glmnet" package. The survival curve ( P<0.001) and ROC curve (AUC>0.75) of the sequence set and verification set were drawn, and the distribution of risk value was visualized. After grouping according to risk value, GSEA enrichment analysis was calculated, gene set grid was constructed, target genes were predicted, and finally, pathway enrichment analysis of GO and KEGG was carried out. Results:387 TFs with different expressions in TCGA and GEO databases were used to draw heat map, volcanic map and TFs-related forest map, and the prognosis model of colon cancer was constructed according to COX multivariate analysis=0.310×HSF4+0.137×IRX3-0.127×ATOH1+0.290×OVOL3+0.137×HOXC6+0.155×SIX2+0.092×ZNF556-0.444×CXXC5+0.429×TIGD1+0.413×TCF7L1. Through enrichment analysis, our results showed that these prognostic factors may directly or indirectly act on cancer pathways, such as basic cell carcinoma and cancer signaling pathway, local tissue-cell adhesion, and extracellular matrix.Conclusions:The constructed TFs prognosis model of colon cancer can quantify the prognostic risk of colon cancer, and its high-risk group is an independent risk factor of colon cancer prognosis. This model is a new way to evaluate the prognosis of colon cancer.
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Objective:To investigate the risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer, and application value of a nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 228 patients with stage Ⅱ-Ⅲ colon cancer who underwent radical resection in the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to June 2016 were collected. There were 118 males and 110 females, aged from 25 to 87 years, with a median age of 62 years. All patients underwent open or laparoscopic-assisted radical resection of colon cancer. Observation indicators: (1) postoperative tumor recurrence; (2) risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer; (3) development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. Follow-up using outpatient examination and telephone interview was performed to detect postoperative 3-year tumor recurrence up to June 2019. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers, and comparison between groups was analyzed using the Pearson chi-square test or Fisher exact probability. Multivariate analysis was performed using Logistic stepwise regression analysis. The independent risk factors were included into R 3.6.1 software to construct a nomogram prediction model. The receiver operating characteristic curve (ROC) was drawed, and the area under curve (AUC) was used to evaluate discrimination of the nomogram prediction model. The calibration chart with R software was used to evaluate consistency of the nomogram prediction model. Results:(1)Postoperative tumor recurrence: 53 of 228 patients had postoperative tumor recurrence including 19 cases with locoregional recurrence and 34 cases with distant metastasis. Of the 34 patients with distant metastasis, there were 14 cases with liver metastasis, 7 cases with lung metastasis, 4 cases with brain metastasis, and 9 cases with multiple metastasis or isolated metastasis in other sites. The time to recurrence was 12 months (range, 6-19 months). (2) Risk factors analysis for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer:results of univariate analysis showed that bowel obstruction, preoperative carcinoembryonic antigen (CEA) level, ascites, vascular invasion were related factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( χ2=4.463, 13.622, 10.914, 5.911, P<0.05). Pathological N stage was also a related factor for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( P<0.05). Results of multivariate analysis showed that preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 were independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer ( odds ratio=3.129, 3.071, 7.634, 3.439, 15.467, 95% confidence interval as 1.328-7.373, 1.047-9.007, 1.103-52.824, 1.422-8.319, 3.498-68.397, P<0.05). (3) Development and evaluation of a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer: based on preoperative CEA level, ascites, vascular invasion and pathological N stage of multivariate analysis, a nomogram prediction model for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was developed using R 3.6.1 software. The nomogram score was 41.7 for preoperative CEA level >5 μg/L, 41.0 for ascites, 74.2 for vascular invasion, 45.1 and 100.0 for pathological N stage as stage N1 and N2, respectively. The total of different scores for risk factors corresponded to the probability of postoperative recurrence. The ROC of nomogram for recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer was drawed,with the AUC of 0.805(95% confidence interval as 0.737-0.873, P<0.05). The calibration chart showed a good consistency between the probability of recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer predicted by nomogram and the actual probability of postoperative recurrence. Conclusions:Preoperative CEA level >5 μg/L, ascites, vascular invasion and pathological N stage as stage N1 or N2 are independent risk factors for tumor recurrence after radical resection of stage Ⅱ-Ⅲ colon cancer. The nomogram prediction model contributes to prediction of the recurrent risks after radical resection of stage Ⅱ-Ⅲ colon cancer.
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Objective@#To evaluate the feasibility and safety of magnetic tracer technique for preoperative endoscopic marking in laparoscopic surgery.@*Methods@#In the preliminary study, a total of 8 patients with gastric (n=3) or colorectal (n=5) tumors underwent endoscopic magnetic marking before laparoscopic surgery from April to June in 2019. First, a magnet was attached to the lesion by 2 titanium clips under the endoscope. Second, during the subsequent laparoscopic operations, the other magnet was sent to the vicinity of the lesion through the laparoscopic tunnel. The magnet in the abdominal cavity was quickly attracted to the one in the gastrointestinal tract to successfully locate the lesions. Data of preoperative marking and operations of 8 patients were reviewed.@*Results@#All 8 lesions were marked successfully, rapid and accurate intraoperative positioning was achieved. The mean time of endoscopic marking was 5.75±2.45 minutes, and the mean time of intraoperative localization was 1.94±0.56 minutes. All patients underwent laparoscopic tumor resections with accurate localization. The mean proximal and distal resection margins of colorectal tumors were 105 mm and 74 mm respectively. No complications occurred.@*Conclusion@#Magnetic tracer technique for laparoscopic localization, simple, safe and accurate for gastrointestinal lesions, can be performed without additional equipment or endoscopic procedures involved.
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Objective To observe the effect of down-regulated CDX2 gene on the migration and invasion abilities of colon cancer cells (SW480 and HT29) and investigate the role and mechanisms of CDX2 gene in occurrence and development of colon cancer metastasis.Methods CDX2 gene in HT29 and SW480 cells was down-regulated using lentivirus RNA interference (RNAi) vector.The interference efficiency of CDX2 was detected by qRT-PCR and Western blotting.The effect of down-regulated CDX2 expression on colon cancer cells'migration and invasion was determined by Transwell and wound heal methods.Then the effects of down-regulated CDX2 on the expressions of epithelial-mesenchymal transition (EMT)-related genes (E-cadherin,ZEB-1,Vimentin,Twist and Snail) were detected by RT-PCR and Western blotting.Results The constructed CDX2 siRNA expression vector could significantly inhibit the expression of CDX2 in HT29 and SW480 cells.Compared with those of the cells transfected with empty vector (LV-NT-shRNA) and non-transfected cells,the migration and invasion abilities of cells transfected with LV-CDX2-shRNA were markedly enhanced (P ＜ 0.05).E-cadherin expression was reduced while expressions of ZEB-1,Vimentin,Twist,and Snail were significantly increased (all P＜0.05).Conclusion Down-regulating the expression of CDX2 can induce the occurrence of EMT,thus enhancing the invasion and migration of colon cancer cells.
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Objective To investigate the clinical characteristics, diagnosis and treatment of primary splenic tumors.Methods The clinical data of 47 patients with spleen tumors treated in the First Affiliated Hospital of Medical College, Xi'an Jiaotong University from January 2008 to October 2014 were retrospectively analyzed.Results 28 patients had no symptoms and only on physical examination was a mass found in some patients.There were 12 patients who manifested with upper abdominal discomfort or pain, 2 patients with an epigastric mass, l patient manifested with fever and 2 patients manifested with nausea and vomiting.Preoperative examination showed anemia in 7 patients.Three patients manifested with hypersplenism.Preoperative ultrasonic examination was performed on 39 patients with a diagnostic rate of 89.7％.43 patients underwent CT examination which had a diagnostic rate of 90.7％, MRI was performed in 4 patients and the diagnoses were all correct.Of the 47 patients with splenic tumor, 38 patients had a benign tumor.34 patients were treated by surgery, including 22 patients who underwent open splenectomy, 9 patients laparoscopic splenectomy, 3 patients laparoscopic fenestration of splenic cyst.Malignant tumors were found in 9 patients.Four patients underwent splenectomy, 2 patients were treated by laparoscopic splenectomy.Preoperative examination and postoperative pathological examination showed a benign tumor in 38 patients, including 1 1 patients with a splenic cyst, 6 patients with a cavernous hemangioma, 5 patients with an inflammatory pseudo tumor of spleen (accounting for 57.3％ of all the benign tumor).Malignant tumors included 5 patients with malignant lymphoma, 1 patient with splenic angiosarcoma, 1 patient with gastric carcinoma which metastasizes to the spleen, 1 patient with cervical carcinoma metastasizing to the spleen and 1 patient with liver carcinoma metastasizing to the spleen.Adjuvant chemotherapy and (or) radiotherapy after surgery were performed for patients with malignant lymphoma of the spleen.For 2 patients who were diagnosed early, surgery combined with radiotherapy or chemotherapy and immunotherapy were alive for more than 18 months.Conclusions The clinical manifestations of splenic tumors lack specificity.The diagnosis mainly depends on ultrasonic examination, CT and MRI.Early diagnosis, radical operation and comprehensive treatment are important to improve the prognosis of patients with malignant tumors of the spleen.
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Objective To construct a adenovirus vector containing human NRP-1 gene and 3Flag gene to interaction between tumor and interstitial cell.Methods Plasmid containing NRP-1 gene was digested by AgeⅠand NheⅠ restriction endonuclease.Then the DNA was ligated into linearized pDC315-3Flag vector.After having been constructed,the pDC3 1 5-NRP-1-3 Flag plasmid was co-transfected with framework plasmid pBHGlox△E1 , 3Cre into HEK 293 cells to obtain the homologous recombinant adenovirus,which was then amplified and purified its titer tested.Expression of NRP-1 protein was detected using Western blot.Results Polymerase chain reaction and sequencing analysis confirmed that the shuttle plasmid pDC3 1 5-NRP-1-3 Flag and design were consistent. Cytopathic effect was observed by inverted phase contrast after transfecting HEK2 9 3 cells with shuttle plasmid pDC315-NRP-1-3Flag.95-130 ku was detected by Western lot after transfecting HEK293 cells with shuttle plasmid pDC315-NRP-1-3Flag and recombinant adenovirus,the size being consistent with the NRP-1-3Flag fusion protein (104 ku),with a titer of 2.00E+11PFU/mL.Conclusion The recombinant adenovirus vector for human NRP-1 gene was successfully constructed expressed in HEK 2 9 3 cells.
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Objective To investigate the effects and mechanisms of sorafenib on hepatic stellate cell viability and activation in the microenvironment of liver tumor.Methods The effects of LX2 cells on HepG2 cell proliferation were observed by coculture of LX2 and HepG2 cells.MTT assay was used to observe the effects of sorafenib on LX2 proliferation,and expression of α-smooth muscle actin (α-SMA) was measured immunocytochemically in LX2 cells treated with different concentrations of sorafenib.Changes in PDGF-BB and TGF-β1 concentrations were detected in LX2 supernatant using ELISA.Expression of ERK1,ERK2,and AKT signaling pathways were measured using Western blot.Furthermore,LX2 cells were cocultured with HepG2 cells for 24 hours to observe their effects on the invasive ability of HepG2 cells.Result After coculture of LX2 and HepG2 cells,HepG2 cells increased in the experimental group more than those of in the control group.After treatment with various concentrations of sorafenib for 12,24,36 or 48 hours,the viability of treated LX2 cells was lower than the controls in a concentration-and time-dependent manner.As sorafenib concentration and time of exposure increased,α-SMA expression became weaker in treated cells.PDGF-BB and TGF-β1 concentrations decreased with higher sorafenib concentrations and with longer exposure under the same concentration.ERK1,ERK2 and Akt expression was identical between treated and control groups,but their phosphorylated expression decreased with increased concentrations of sorafenib.The invasive ability of HepG2 cells induced by LX2 gradually decreased as sorafenib concentrations increased.Conclusions Sorafenib suppressed α-SMA expression,inhibited PDGF-dependent signaling pathways in HSCs,downregulated PDGF-BB and TGF β1 expression in the supernatant of HSCs,and restrained the viability and activation of HSCs.Sorafenib treatment therefore resulted in suppressed proliferation and invasion of HepG2 cells.
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To discuss the status quo of gallbladder cancer in China,88 articles published in China were collected and the clinical data of 7882 patients who were suffering from gallbladder cancer was analyzed.The requirements for the literature were:domestic articles published from 1980.1 to 2008.6,the gallbladder cancer cases must exceed 50,the cases must come from the same domestic hospital,and if the cases were reduplicative,the maximum were selected.Analysis of the data showed that primary carcinoma of the gallbladder was the most common malignant tumor in the biliary tract,with a higher incidence in females than males.The cancer's pathologic characteristics of undiscoverable growth and poor differentiation led to its clinical significance of difficult early stage diagnosis,high degree of malignancy,poor prognosis,and adenocarcinoma formation.Although the technique of surgical operation has constantly progressed over time,gallbladder cancer surgery possesses a lower rate of radical resection.Every biliary surgeon should brainstorm and deliberate about how to face the status quo of gallbladder cancer in China.This article participates in that discussion by identifying several noticeable problems in the diagnosis and treatment of gallbladder cancer.
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Objectives To analyze the relationship between the multi-organ hypoxia damage and the death of acute high altitude sickness severe case. Methods 3220 cases from 1956. 06 to 2005.06 in the hospital were reviewed by questionnaire and the cases in MODS or death were screened out. The cause of death and feature were analyzed by the data as clinical symptom, physical signs and auxiliary examination. Results 281 cases complicated by MODS (include 35 dead cases) were found out by review. The incidence with MODS is 8.73% , and the death rate was 1.09%. The masculine incidence rate of the clinical symptom, physical signs and auxiliary examination in death were 2. 86% ~65. 71% , 2. 86% ~ 100% and 14. 29% ~ 100% , respectively. The MODS incidence in dead cases was 100%. Compared with the curing group, the MODS number, cardiac functional disturbance, brain disorder and renal functional disturbance in the death group had a significantly high incidence rate in all the 281 cases with MODS( P <0.05). With dependability analysis, there were a significantly direct correlation relationship between the death in the severe cases with acute high altitude sickness and the number of MODS ( r = 0. 3473, P < 0.001). Conclusion Hypoxia to the damage of multi-organ function play an important role in death of the severe cases with acute high altitude sickness in high attitude area, and the functional disturbance of important organs as heart, brain and kidney is the most important cause to death.
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Gallbladder volvulus is defined as the rotation of the gallbladder on its mesentery along the axis of the cystic duct and cystic artery. It is an unusual and rare occurrence with a predilection for women in their sixth or eighth decades of life. Only about 400 cases have been reported in the literature. The etiology of gallbladder volvulus remains speculative; however, the presence of a redundant mesentery is a prerequisite for torsion. Clinical symptoms are non-specific. Some form of right upper quadrant abdominal pain is nearly always present. Although recent advances in radiographic studies have aided in the diagnosis of many diseases,radiographic studies remain nonspecific in diagnosing gallbladder torsion. Laboratory evaluations are often nonspecific. An elevated white blood cell count is a frequent finding.Liver function tests are commonly normal. Gallbladder volvulus leads to gangrene or perforation because of occlusive obstruction of biliary drainage and blood flow. With early diagnosis and surgical intervention, the disease maintains a low mortality. Here, we present a review of the literature about gallbladder volvulus in order to enhance recognition of gallbladder volvulus.
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Objective To investigate the protective effect of felodipine on reactive oxygen species (ROS) generation,mRNA level of inflammatory factors such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1),in human umbilical vein endothelial cells (HUVECs) injured by oxidized low-density lipoprotein (ox-LDL) so as to explore felodipine's anti-atherosclerosis mechanism independent of its anti-hypertensive effect. Methods Isolated HUVECs were treated with ox-LDL at different concentrations (6,12.5 and 25 mg/L) for 24 hours so that the optimal concentration and time of ox-LDL treatment were selected. Then the cells were incubated with ox-LDL and treated with felodipine at different concentrations (0.1,1 and 10 ?mol/L). Intracellular ROS level was determined by flow cytometry (FCM). Expressions of inflammatory factors ICAM-1 and VCAM-1 were measured by real time-polymerase chain reaction (real time-PCR). Results ROS generation was increased in HUVECs after treatment with different concentrations (6,12.5 and 25 mg/L) of ox-LDL for 24 hours and there was a significant difference at 25 mg/L ox-LDL (P
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Objective To investigate the protective effects of felodipine on mRNA levels of endothelial nitricoxide synthase (eNOS) and inducible nitricoxide synthase (iNOS) as well as the level of nitrogen monoxidum (NO) from human umbilical vein endothelial cells (HUVECs) injuryed by oxidized low density lipoprotein (ox-LDL). Methods Isolated HUVECs were divided into blank control group,ox-LDL injury group treated with ox-LDL of different concentrations (6,12.5 and 25 mg/L),and intervention group of felodipine (0.1,1.0 and 10 ?mol/L)+ox-LDL (25 mg/L). Then eNOS and iNOS expressions were measured by real time-polymerase chain reaction and the level of NO in the supernatants of the cultures was assayed by nitrate reductase method. Results The mRNA expressions of eNOS and iNOS in HUVECs and NO level in the supernatants during treatment with different ox-LDL concentrations were higher than those in control group. However,felodipine significantly down-regulated the expression of iNOS in HUVECs injured by ox-LDL and inceased NO generation. Conclusion Felodipine has protective effects on endothelial cells. The mechanism may be related to its lowering the mRNA expression of iNOS induced by low ox-LDL concentration and increasing NO production.