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Background: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker.Methods: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort.Results: Upon activation the expression of TGF-β and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885-0.964; p = 0.000).Conclusions: A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: The CAO/ARO/AIO-94 demonstrated that neoadjuvant chemoradiotherapy (CRT) could decrease the rate of local recurrence rather than distal metastases in advanced rectal cancer. Adjuvant chemotherapy (ACT) can eliminate micrometastasis, and render a better prognosis to rectal cancer. However, adoption of ACT mainly depends on the evidence from colon cancer. Neoadjuvant CRT can lead to tumor shrinkage in a number of patients with advanced rectal cancer. The administration of adjuvant therapy depending on pretreatment clinical stage or postoperative yield pathological (yp) stage remains controversial. At present, the clinical guidelines recommend ACT for patients with stage II/III (ypT3-4 N0 or ypTanyN1-2) rectal cancer following neoadjuvant CRT and surgery. However, the yp stage may influence the guidance of ACT.Methods: According to the postoperative pathological stage, the present study was divided into two parts with different study design procedures. Patients will undergo different therapeutic strategies after collecting data related to postoperative pathological stage. For patients with pathologic complete response or yp stage I, the study was designed as a non-inferiority trial to compare the patients' long-term outcomes in observational group and those in treatment group with 5-fluorouracil. For patients at yp stage II or III, the study was designed as a superiority trial to compare the oncological effect of oxaliplatin combined with 5-fluorouracil, in addition to 5-fluorouracil alone in ACT. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints are 3-year, 5-year overall survival, 5-year DFS, and the rate of local recurrence and adverse events resulted from chemotherapy and the patients' quality of life postoperatively.Discussion: The ACRNaCT trial aims to investigate whether observation is not inferior than 5-fluorouracil for pathologic complete response or yp stage I, and indicate whether combined chemotherapy contains superior outcomes than 5-fluorouracil alone for yp stage II or III in patients receiving neoadjuvant CRT and surgery for locally advanced rectal cancer (LARC). This trial is expected to provide individualized adjuvant treatment strategies for LARC patients following neoadjuvant CRT and surgery.Trial Registration: The trial has been registered in ClinicalTrials.gov on January 30, 2018 (Registration No. NCT03415763), and also, that was registered in Chinese Clinical Trial Registry on November 12, 2018 (Registration No. ChiCTR1800019445). [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis disease activity is determined by measuring symptoms and signs. Our aim was to determine which symptom domains are frequent and responsive to change in the evaluation of disease activity, which are those defined by three criteria: 1) they occur frequently during flares; 2) they improve during effective therapy for ulcerative colitis; and 3) they resolve during remission.Methods: Twenty-eight symptom domains, 16 from standard indices and 12 novel domains identified by ulcerative colitis patient focus groups, were evaluated. Sixty subjects with ulcerative colitis were surveyed, rating each symptom on the three criteria with a 100 mm Visual Analogue Scale. Frequent and responsive symptoms were defined a priori as those whose median Visual Analogue Scale rating for all 3 criteria was significantly greater than 50.Results: Thirteen of the 28 symptom domains were identified as both frequent in ulcerative colitis flares and responsive to changes in disease activity. Seven of these 13 symptom domains were novel symptoms derived from ulcerative colitis patient focus groups including stool mucus, tenesmus, fatigue, rapid postprandial bowel movements, and inability to differentiate liquid or gas from solid stool when rectal urgency occurs. Ten of the 16 symptom domains from standard indices were either infrequent or unresponsive to changes in disease activity.Conclusion: Only some of the symptoms of ulcerative colitis that are important to patients are included in standard indices, and several symptoms currently measured are not frequent or responsive to change in ulcerative colitis patients. Development of survey measures of these symptom domains could significantly improve the assessment of disease activity in ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation.Methods: Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities.Results: Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively.Conclusions: This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study. [ABSTRACT FROM AUTHOR]

Aim: This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer.Materials and Methods: Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1-5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1-14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test.Results: A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS.Conclusion: An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients with locally advanced rectal cancer, and produces a high rate of pCR. A prognostic score model is helpful to distinguish different long-term prognosis groups in early stage. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer.Methods and Materials: From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed.Results: With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0-1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2-3 group with no statistical significance (P = 0.873).Conclusions: An elevated baseline NLR is a valuable and easily available prognostic factor for OS in addition to tumor response after neoadjuvant therapy. Baseline NLR could be a useful candidate factor for stratifying patients and making treatment decisions in locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Neoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC.Methods and Materials: Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m² d1 weekly) and capecitabine (625 mg/m² b.i.d. d1-5 weekly). One cycle of capecitabine (1000 mg/m² b.i.d. d1-14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation.Results: Between October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2-3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3-4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1-2.Conclusions: Our study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical complications. Treatment response was an early surrogate marker and correlated to oncologic prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and outcomes of radiotherapy (RT) or chemoradiotherapy (CRT) in elderly patients (≥70) with rectal cancer.Methods: Elderly patients aged 70 and older with rectal cancer, who were treated with RT or CRT at a single institution, were retrospectively analyzed. Performance status (KPS and ECOG score) and comorbidity (Charlson comorbidity index) were calculated, and their correlation with treatment toxicity and overall survival were studied. Risk factors for overall survival were investigated using univariate and multivariate survival analysis.Results: A total of 126 patients with locally advanced disease, local recurrence or synchronous metastasis were included, with a 3-year OS rate of 48.1%. Scheduled dosage of radiation was delivered to 69% of patients. Grade 3 toxicities occurred more often in patients treated with CRT versus RT. The occurrence of grade 3 toxicities was not related to KPS score, ECOG score, number of comorbidities, and Charlson score. Multivariate analysis found that only age and Charlson score were independent prognostic factors for predicting patients' 3-year OS. The 3-year OS rate was significantly higher in patients with Charlson score <4 vs Charlson score ≥4 (71.1% vs. 26.4%, P=0.0003).Conclusions: Although toxicities may be significant, elderly patients with rectal cancer of varied stages can be safely treated with RT or CRT with careful monitoring and frequent modification of treatment. Except for patients' age, Charlson comorbidity index may be helpful in assessing patients' outcomes in elderly patients with rectal cancer. [ABSTRACT FROM AUTHOR]

Background: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABA A receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABA A Rγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1., Methods: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABA A Rγ2 protein expression in hepatocellular carcinoma. In vivo tumorigenticity test was conducted in nude mice by regulation the expression of Nova1. Later, western blot and co-immunoprecipitation were carried out to verify the interaction between Nova1 and GABA A Rγ2 in HCC tissue., Results: Immunohistochemical staining showed GABA A Rγ2 expression in HCC. Survival analysis showed intratumoral GABA A Rγ2 was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Up-regulation of Nova1 expression promotes subcutaneous HCC growth in nude mice and western blot showed the ectopic expression of Nova-1 restro-regulates the expression of GABA A Rγ2 and GABA. Protein level interaction of GABA A Rγ2 and Nova-1 was evidenced by co-immunoprecipitation., Conclusions: Nova1 interacts with GABA A Rγ2 not only in CNS but also in HCC. Nova1's potential mechanism as an oncogene may due to its interaction with GABA A Rγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.

Background: This study was conducted to investigate the local effects and toxicity of accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation., Methods: Twenty-two patients with recurrent/unresectable rectal cancer who previously received pelvic irradiation were enrolled in our single-center trial between January 2007 and August 2012. Reirradiation was scheduled for up to 39 Gy in 30 fractions using intensity-modulated radiotherapy plans. The dose was delivered via a hyperfractionation schedule of 1.3 Gy twice daily. Patient follow-up was performed by clinical examination, CT/MRI, or PET/CT every 3 months for the first 2 years and every 6 months thereafter. Tumor response was evaluated 1 month after reirradiation by CT/MRI based on the RECIST criteria. Adverse events were assessed using the National Cancer Institute (NCI) common toxicity criteria (version 3.0)., Results: The median time from the end of the initial radiation therapy to reirradiation was 30 months (range, 18-93 months). Overall local responses were observed in 9 patients (40.9%). None of the patients achieved a complete response (CR), and 9 patients (40.9%) had a partial response (PR). Thirteen patients failed to achieve a clinical response: 12 (54.5%) presented with stable disease (SD) and 1 (4.5%) with progressive disease (PD). Among all the patients who underwent reirradiation, partial or complete symptomatic relief was achieved in 6 patients (27.3%) and 13 patients (59.1%), respectively. Grade 4 acute toxicity and treatment-related deaths were not observed. The following grade 3 acute toxicities were observed: diarrhea (2 patients, 9.1%), cystitis (1 patient, 4.5%), dermatitis (1 patient, 4.5%), and intestinal obstruction (1 patient, 4.5%). Late toxicity was infrequent. Chronic severe diarrhea, small bowel obstruction, and dysuria were observed in 2 (9.1%), 1 (4.5%) and 2 (9.1%) of the patients, respectively., Conclusions: This study showed that accelerated hyperfractionated intensity-modulated radiotherapy significantly relieved local symptoms and led to a promising local response with an acceptable toxicity profile in patients with recurrent/unresectable rectal cancer and previous pelvic irradiation. Innovative treatment regimens should be evaluated in future studies to improve the clinical outcome while avoiding excessive toxicity in patients with recurrent rectal cancer and previous pelvic irradiation.

Background: The treatment of hypertensive spontaneous intracranial hemorrhage (ICH) is still controversial. The purpose of the present study was to investigate whether minimally invasive puncture and drainage (MIPD) could improve patient outcome compared with decompressive craniectomy (DC)., Methods: Consecutive patients with ICH (≧30 mL in basal ganglia within 24 hours of ictus) were non-randomly assigned to receive MIPD (group A) or DC (group B) hematoma evacuation. The primary outcome was death at 30 days after onset. Functional independence was assessed at 1 year using the Glasgow Outcome Scale., Results: A total of 198 patients met the per protocol analysis (84 in group A and 114 in group B). The initial Glasgow Coma Scale (GCS) score was 8.1 ± 3.4 and the National Institutes of Health Stroke Scale (NIHSS) score was 20.8 ± 5.3. The mean hematoma volume (HV) was 56.7 ± 23.0 mL, and there was extended intraventricular hemorrhage (IVH) in 134 patients. There were no significant intergroup differences in the above baseline data, except group A had a higher mean age than that of group B (59.4 ± 14.5 vs. 55.3 ± 11.1 years, P = 0.025). The cumulative mortalities at 30 days and 1 year were 32.3% and 43.4%, respectively, and there were no significant differences between groups A and B. However, the mortality for patients ≦60 years, NIHSS < 15 or HV≦60 mL was significantly lower in group A than that in group B (all P < 0.05). The cumulative functional independence at 1 year was 26.8%, and the difference between group A (33/84, 39.3%) and group B (20/114, 17.5%) was significant (P = 0.001). Multivariate logistic regression analysis showed that a favorable outcome after 1 year was associated with the difference in therapies, age, GCS, HV, IVH and pulmonary infection (all P <0.05)., Conclusions: For patients with hypertensive spontaneous ICH (HV≧30 mL in basal ganglia), MIPD may be a more effective treatment than DC, as assessed by a higher rate of functional independence at 1 year after onset as well as reduced mortality in patients ≦60 years of age, NIHSS < 15 or HV≦60 mL.

Aims: Based on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy., Materials and Methods: Thirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group)., Results: The toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4-23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274)., Conclusion: It was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy.

Background: Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively., Methods: A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS)., Results: The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00)., Conclusions: The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.

Using the North American Rheumatoid Arthritis Consortium genome-wide association dataset, we applied ridged, multiple least-squares regression to identify genetic variants with apparent unique contributions to variation of anti-cyclic citrullinated peptide (anti-CCP), a newly identified clinical risk factor for development of rheumatoid arthritis. Within a 2.7-Mbp region on chromosome 6 around the well studied HLA-DRB1 locus, ridge regression identified a single-nucleotide polymorphism that was associated with anti-CCP variation when including the additive effects of other single-nucleotide polymorphisms in a multivariable analysis, but that showed only a weak direct association with anti-CCP. This suggests that multivariable methods can be used to identify potentially relevant genetic variants in regions of interest that would be difficult to detect based on direct associations.

Background: Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now., Results: Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence., Conclusion: As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.