Objective:To investigate the risk factors for lymph node metastasis in T1 colorectal cancer and application value of its nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 914 patients with T1 colorectal cancer who underwent radical resection in the Zhongshan Hospital of Fudan University from June 2008 to December 2019 were collected. There were 528 males and 386 females, aged from 25 to 87 years, with a median age of 63 years. Observation indicators: (1) clinicopathological data of patients with T1 colorectal cancer; (2) follow-up; (3) analysis of influencing factors for lymph node metastasis; (4) development and internal validation of a nomogram predition model. Patients were regularlly followed up once three months within postoperative 2 years and once six months thereafter to detect tumor recurrence and survival. The endpoint of follow-up was at postoperative 5 years. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Logistic regression analysis. Based on results of multivariate analysis, a Logistic regressional nomogram for prediction of lymph node metastasis probability was constructed using R language software. The calibration curve was used to evaluate the consistency between probability predicted by the nomogram model and actual observation probability, which was reprensented by a consistency index. The Bootstrap method was used for evaluation of the model performance to receive the calibration curve. The Hosmer-Lemeshow test was used to calculate the goodness of fit in model. Results:(1) Clinicopathological data of patients with T1 colorectal cancer: 687 of 914 patients underwent direct surgery and 227 underwent remedial operation after endoscopic resection. All the 914 patients were confirmed as pT1NxM0 colorectal cancer by pathological examination. The tumor diameter was (2.3±1.2)cm. The pathological catogaries of 914 patients included 865 cases of adenocarcinoma and 49 cases of mucinous adenocarcinoma. The tumor differentiation degree of 914 patients included 727 cases of high or middle differentiation and 187 cases of low differentiation or undifferentiation. Of the 914 patients, 633 cases had submucosal infiltration depth ≥1 000 μm and 281 cases had submucosal infiltration depth <1 000 μm. There were 110 cases with nerve vessel invasion and 804 without nerve vessel invasion. The number of intraoperative lymph node dissection was 13 (range, 1-48). There were 804 cases in stage N0 of N staging, 98 cases in stage N1 and 12 cases in stage N2. There was no perioperative death. (2) Follow-up: 886 of 914 patients were followed up for 25 months (range, 1-129 months). During the follow-up, 24 patients had tumor recurrence or metastasis. The 5-year cumulative tumor recurrence rate of 914 patients was 4.8% and the median recurrence time was 17.0 months. Liver was the main site of tumor recurrence, accounting for 58.3%(14/24). The 5-year recurrence-free survival rate of 914 patients was 95.2%. The 5-year recurrence-free survival rate was 96.3% of 804 patients without lymph node metastasis, versus 86.6% of 110 patients with lymph node metastasis, showing a significant difference between the two groups ( χ2=6.83, P<0.05). (3) Analysis of influencing factors for lymph node metastasis: results of univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative CA19-9, tumor differentiation degree, submucosal infiltration depth, nerve vessel invasion were related factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.56, 3.25, 2.21, 2.68, 3.39, 95% confidence interval as 1.41-4.67, 1.22-8.66, 1.43-3.41, 1.56-4.88, 2.10-5.48, P<0.05). Results of multivariate analysis showed that preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥1 000 μm and nerve vessel invasion were independent risk factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.23, 3.47, 2.01, 2.31, 2.91, 95% confidence interval as 1.02-4.15, 1.08-10.87, 1.03-3.27, 1.40-4.47, 1.64-5.13, P<0.05). (4) Development and internal validation of a nomogram predition model: based on results of multivariate Logistic analysis, a nomogram prediction model for lymph node metastasis in T1 colorectal cancer was developed. The nomogram score was 59 for preoperative CEA >5 μg/L, 100 for preoperative CA19-9 ≥37 U/mL, 48 for poor differentiation or undifferentiation, 67 for submucosal infiltration depth ≥1 000 μm and 92 for nerve vessel invasion, respectively. The total of different scores for different clinicopathological factors corresponded to the probability of lymph node metastasis. The receiver operating characteristic curve was drawed to evaluate the predictive performance of nomogram for lymph node metastasis in T1 colorectal cancer, with the area under curve of 0.70(95% confidence interval as 0.64-0.75, P<0.05). The Bootstrap internal validation of predictive performance in the nomogram predition model showed a consistency index of 0.70 (95% confidence interval as 0.65-0.75). The calibration chart showed a good consistency between the probability predicted by the nomogram model and actual probability of lymph node metastasis. The Hosmer-Lemeshow test showed a good fitting effect in model ( χ2=1.61, P>0.05). Conclusions:Preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥ 1 000 μm and nerve vessel invasion are independent risk factors for lymph node metastasis in T1 colorectal cancer. The constructed nomogram model can help predict the probability of lymph node metastasis in T1 colorectal cancer.

Background: Coinfection with avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) is common in chickens, and the molecular mechanism of the synergistic pathogenic effects of the coinfection is not clear. Exosomes have been identified as new players in the pathogenesis of retroviruses. The different functions of exosomes depend on their cargo components. Objectives: The aim of this study was to investigate the function of co-regulation differentially expressed proteins in exosomes on coinfection of ALV-J and REV. Methods: Here, viral replication in CEF cells infected with ALV-J, REV or both was detected by immunofluorescence microscopy. Then, we analyzed the exosomes isolated from supernatants of chicken embryo fibroblast (CEF) cells single infected and coinfected with ALV-J and REV by mass spectrometry. KEGG pathway enrichment analyzed the co-regulation differentially expressed proteins in exosomes. Next, we silenced and overexpressed tripartite motif containing 62 (TRIM62) to evaluate the effects of TRIM62 on viral replication and the expression levels of NCK-association proteins 1 (NCKAP1) and actin-related 2/3 complex subunit 5 (ARPC5) determined by quantitative reverse transcription polymerase chain reaction. Results: The results showed that coinfection of ALV-J and REV promoted the replication of each other. Thirty proteins, including TRIM62, NCK-association proteins 1 (NCKAP1, also known as Nap125), and Arp2/3-5, ARPC5, were identified. NCKAP1 and ARPC5 were involved in the actin cytoskeleton pathway. TRIM62 negatively regulated viral replication and that the inhibition of REV was more significant than that on ALV-J in CEF cells coinfected with TRIM62. In addition, TRIM62 decreased the expression of NCKAP1 and increased the expression of ARPC5 in coinfected CEF cells. Conclusions Collectively, our results indicated that coinfection with ALV-J and REV competitively promoted each other's replication, the actin cytoskeleton played an important role in the coinfection mechanism, and TRIM62 regulated the actin cytoskeleton.

Objective To investigate the clinical characteristics and mechanism of cavernous sinus dural arteriovenous fistula (CSDAVF). Methods The clinical data of 17 CSDAVF patients, including clinical manifestations, characteristics of cerebrospinal fluid (CSF)and neuroimaging,were analyzed.The interventional catheter embolization of CSDAVF and postoperative follow-up were performed. Results Of the 17 subjects with CSDAVF, 5 (29.4%) were men and 12 (70.6%)were women (sex ratio=1:2.4).The average age of onset was (58.12±14.61)years old. Older CSDAVF patients were prone to be complicated with hypertension than general population at the same age. Onset symptoms included headache in 6 cases,eye symptoms in 5 cases,intracranial murmur in 2 cases,diplopia in 2 cases, dizziness in 1 case and slurred speech in 1 case. Digital subtraction angiography (DSA) was performed in all 17 patients. Further embolization was applied in 14 patients and had satisfactory outcome. In CSDAVF patients with headache, 2 patients showed orthostatic headache as initial symptom. One of them with intracranial hypotension reported exophthalmos 3 months after the onset. Those two patients remained asymptomatic during 3-year and 2-year follow-up after receiving interventional catheter embolization for CSDAVF. Conclusions CSDAVF usually occurs in middle-aged and older women, especially in those with hypertension. CSDAVF varies in clinical manifestations. A special attention should be given to orthostatic headache which can be presented as the initial symptom in few patients with CSDAVF. CTA or DSA should be considered in patients with clinically suspected CSDAVF to rule out the possibility of CSDAVF. The interventional catheter embolization is the primary treatment of CSDAVF.