Timing and Origins of Local and Distant Metastases in Lung Cancer.

INTRODUCTION: Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive. METHODS: We performed whole-exome sequencing for 40 primary tumors (PTs) and 61 metastases from 47 patients with lung cancer, of which 40 patients had paired PTs and metastases. The PT-metastasis genomic divergence, metastatic drivers, timing of metastatic dissemination, and evolutionary origins were analyzed using appropriate statistical tools and mathematical models. RESULTS: There were various degrees of genomic heterogeneity when comparing the paired primary and metastatic lesions or comparing metastases of different sites. Multiple metastasis-selected/enriched genetic alterations were found, such as MYC amplification, NKX2-1 amplification, RICTOR amplification, arm 20p gain, and arm 11p loss, and these results were were also featured in a meta-analysis cross-validated using an independent cohort from Memorial Sloan-Kettering Cancer Center database. To elucidate the metastatic seeding time, we applied a metastatic model and found 61.1% of the tumors were late dissemination, in which the metastatic seeding happened approximately 2.74 years before clinical detection. One exception was lymph node metastases whose dissemination time was relatively early. By analyzing the evolutionary origins, we reported that nonlymph node metastases were mainly seeded by the PT (87.5%) rather than the earlier colonized lymph node metastases. CONCLUSIONS: Our results shed light on the molecular features that potentially drive lung cancer metastases. The distinct temporospatial pattern of disease progression revealed that lung cancer was susceptible to either late dissemination or indolent early lymph node metastases, leaving a potential time window to minimize metastases by early cancer detection.

Intron Retention as a Mode for RNA-Seq Data Analysis.

Intron retention (IR) is an alternative splicing mode whereby introns, rather than being spliced out as usual, are retained in mature mRNAs. It was previously considered a consequence of mis-splicing and received very limited attention. Only recently has IR become of interest for transcriptomic data analysis owing to its recognized roles in gene expression regulation and associations with complex diseases. In this article, we first review the function of IR in regulating gene expression in a number of biological processes, such as neuron differentiation and activation of CD4+ T cells. Next, we briefly review its association with diseases, such as Alzheimer's disease and cancers. Then, we describe state-of-the-art methods for IR detection, including RNA-seq analysis tools IRFinder and iREAD, highlighting their underlying principles and discussing their advantages and limitations. Finally, we discuss the challenges for IR detection and potential ways in which IR detection methods could be improved.

RETRACTED: Effect of transplantation of BMMSCs on pathological change of gastric precancerous lesions of rats.

OBJECTIVE: To build the rat model of gastric precancerous lesions and discuss the effect of transplantation of mesenchymal stem cells (BMMSCs) on the pathological change. METHODS: The rat model of gastric precancerous lesions was built using N-methyl-N'-nitro-N'-nitrosoguanidine. After the intravenous transplantation of BMMSCs, the migration and colonization location was then observed, as well as its effect on the related factors of gastric precancerous lesions, including VEGF, IL-10 and IFN-γ. RESULTS: BMMSCs were mainly colonized in the gastric body and gastric antrum, which could be differentiated into the epithelial and interstitial cells. The expression of VEGF in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05); while the expression of VEGF in the transplantation group was significantly higher than that in the non-transplantation group (t = 3.88, P < 0.001). The expression of serum IL-10 and IFN-γ in the transplantation group and non-transplantation group was significantly higher than that in the control group (P < 0.05), while the expression of IL-10 and IFN-γ in the transplantation group was significantly lower than that in the non-transplantation group (t = 3.03, P = 0.004; t = 3.80, P < 0.001). CONCLUSIONS: BMMSCs can be directionally differentiated into the epithelial and interstitial cells and can also regulate the related growth factors and inflammatory factors to reduce the injury of inflammation, relieve or reverse the process of gastric precancerous lesions.

[Risk factors associated with postoperative complications after reoperation for recurrent Crohn disease].

OBJECTIVE: To evaluate the risk factors of postoperative complications after reoperation for recurrent Crohn disease(CD). METHODS: From 1995 to 2009, 65 patients undergoing reoperation for recurrent CD were identified in the First Affiliated Hospital of Fujian Medical University. Risk factors of postoperative complications were analyzed. These patients were matched by age to 65 patients undergoing primary operation and treatment outcomes were compared between primary operation and reoperation. RESULTS: Postoperative complications were observed in 25 cases(38.5%) undergoing reoperation for CD recurrence and the rate of postoperative complication was higher than that after primary operation(12.3%). Postoperative complications rate in patients with stoma was significantly lower than those without stoma(15.8% vs. 47.8%, χ(2)=5.831, P=0.016). Compared to primary operation, reoperation had longer operative time, more severe intraperitoneal adhesion, and a longer postoperative hospital stay(all P<0.05). CONCLUSION: Reoperation for CD recurrence is associated with higher postoperative complications. Temporary stoma may decrease the rate of postoperative complication.

[Safety and efficacy on cerebral protection with filter devices during carotid artery stenting in Chinese patients].

OBJECTIVE: To assess the efficacy, safety, procedural success and long-term clinical outcome in patients underwent percutaneous carotid stenting with distal device. METHODS: Percutaneous carotid stents with distal device were implanted to 58 patients with 59 significant (> 75%) carotid artery stenosis (49 men, mean age 68 years) between January 2000 to December 2005. Forty-five out of 58 patients were symptomatic, 35 had coronary artery diseases and 10 had previous strokes. RESULTS: Sixty one carotid stenting were implanted to 59 lesions in 58 patients. Stents with filter devices were successfully implanted in 57 out of 58 (98%) patients. Angioplasty success rate was 100%. Aspirin (300 mg/d) and Clopidogrel (75 mg x 2/d) were administered 3 days prior operation and clopidogrel was discontinued 30 days post stenting and aspirin was continued at dose of 100 mg/d. The percentage of stenotic carotid artery reduced from 85.3% to 6.2% after stenting and the diameter increased from 1.3 +/- 0.9 mm to 5.2 +/- 1.1 mm. Two minor strokes (3.4%) occurred during operation and at 14 days post stenting. All patients were discharged from the hospital after an average of 2.5 days hospitalization. At 14 +/- 2 months follow up, all patients survived and there were 2 asymptomatic restenosis (50% and 70% and the latter underwent successful balloon angioplasty), 2 myocardial infarctions (1 non-Q wave and 1 Q wave myocardial infarction, all underwent successful emergent PCI) and 2 minor strokes occurred at 6 and 8 months post stenting. CONCLUSION: Carotid stenting with distal device appears to be safe and effective in treating patients with carotid artery stenosis.

Safety and efficacy of carotid artery stenting.

OBJECTIVE: To evaluate the safety and efficacy of carotid artery stenting (CAS). METHODS: We prospectively evaluated the safety and efficacy of 76 carotid artery stenting (CAS) procedures in a consecutive series of 70 Chinese patients. This series represented a high-risk group that included patients with unstable angina, previous ipsilateral CEA, contralateral carotid artery occlusion, post-radiation carotid artery stenosis and other severe co-morbid conditions. The patients had independent neurological examinations before and after the procedure and follow-up cerebral angiography at 6 month. RESULTS: The procedural success rate was 100%. The mean carotid artery stenosis was (82+/-18) % before and (5+/-10) % after the procedure. During the initial hospital period and 30 days after CAS, there was no major stroke but 3 minor strokes (5.7%). No myocardial infarctions or deaths occurred during or within 30 days following CAS. At a mean follow-up of 20+/-12 months, 2 patients (2.8%) had asymptomatic restenosis, and 2 non-Q wave myocardial infarction. Death occurred in 2 cases, but none of them was attributed to a neurological cause. Three patients had minor strokes and no major strokes occurred during the follow-up period. CONCLUSION: Percutaneous carotid artery stenting is feasible for performance in Chinese patients and may lower the restenosis rate.