Publications by authors named "Yanling Ren"

38 Publications

Sustained Auditory Attentional Load Decreases Audiovisual Integration in Older and Younger Adults.

Neural Plast 2021 17;2021:4516133. Epub 2021 Jun 17.

Department of Psychology, Faculty of Education, Hubei University, Wuhan 430062, China.

The modulation of attentional load on the perception of auditory and visual information has been widely reported; however, whether attentional load alters audiovisual integration (AVI) has seldom been investigated. Here, to explore the effect of sustained auditory attentional load on AVI and the effects of aging, nineteen older and 20 younger adults performed an AV discrimination task with a rapid serial auditory presentation task competing for attentional resources. The results showed that responses to audiovisual stimuli were significantly faster than those to auditory and visual stimuli (AV > V ≥ A, all < 0.001), and the younger adults were significantly faster than the older adults under all attentional load conditions (all < 0.001). The analysis of the race model showed that AVI was decreased and delayed with the addition of auditory sustained attention (no_load > load_1 > load_2 > load_3 > load_4) for both older and younger adults. In addition, AVI was lower and more delayed in older adults than in younger adults in all attentional load conditions. These results suggested that auditory sustained attentional load decreased AVI and that AVI was reduced in older adults.
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http://dx.doi.org/10.1155/2021/4516133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225455PMC
June 2021

Whole exome sequencing reveals a novel LRBA mutation and clonal hematopoiesis in a common variable immunodeficiency patient presented with hemophagocytic lymphohistiocytosis.

Exp Hematol Oncol 2021 Jun 13;10(1):38. Epub 2021 Jun 13.

Myelodysplastic Syndromes Diagnosis and Therapy Center, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Common variable immunodeficiency (CVID) was a kind of primary immunodeficiency disorders with heterogeneous phenotype and genotype. Lipopolysaccharide-responsive and beige-like anchor (LRBA) mutation was identified as disease associated in CVID, advanced genetic method will help to detect atypical cases. We report a case of adult patient manifested as hemophagocytic lymphohistiocytosis (HLH), bone marrow examination suggested prosperity to MDS, manifested as increased immature myeloid cells and dysplastic hematopoiesis. Whole exome sequencing (WES) identified a novel heterogeneous c.1876T > C (p.W626R) mutation in LRBA and four somatic mutations: ASXL1 (c.1967dupA); PTPN11 (c.226G > A), U2AF1 (c.101C > T and c.470A > G), among which ASXL1 was a high-risk marker of clonal hematopoiesis. Combined with her recurrent severe infections and immune abnormalities such as hypoimmunoglobulinemia, the patient was diagnosed with CVID. Subsequent hematopoietic stem cell transplantation saved her from severe cytopenia and immune deficiency. This case report highlights the great promise of utilization of WES for diagnosing rare disease with atypical manifestations and guiding further treatment.
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http://dx.doi.org/10.1186/s40164-021-00229-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201866PMC
June 2021

Lower-dose decitabine improves clinical response compared with best supportive care in lower-risk MDS patients: a prospective, multicenter phase 2 study.

J Cancer 2021 19;12(10):2975-2981. Epub 2021 Mar 19.

MDS Center, Department of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.

To explore the efficacy and safety of lower-dose decitabine in patients with lower-risk MDS, a prospective multicenter phase II study was conducted to compare decitabine with the best supportive care (BSC). Patients diagnosed with lower-risk MDS from September 2013 to August 2018 were assigned to the decitabine group or the BSC group. Decitabine (12 mg/m/day) was administered over 1 hour/day for 5 consecutive days in a 4-week cycle. BSC, including growth factors, transfusion, thalidomide, lenalidomide, and immunosuppressive agents were given consecutively. The endpoints included the proportion of patients who achieved overall response (OR) in the first 2 or 3 courses, event-free survival (EFS), and overall survival (OS). A total of recruited 82 patients were analyzed. In the decitabine group, 65.9% (27/41) achieved OR after 2 or 3 cycles of treatment, compared with 22.0% (9/41) in the BSC group (p <0.01). Besides, 44.0% (11/25) in the decitabine group became independent of RBC/Platelets transfusion, compared with 27.8% (5/18) in the BSC group. Patients with gene mutation and treated with decitabine achieved a higher OR rate, compared with those without gene mutation [72.0% (18/25) vs 11.5% (3/26), p <0.01]. There was no significant difference in the median EFS between the decitabine and BSC groups (20.6 vs 14.3 months respectively, p = 0.665). In the decitabine group, the most significant adverse events were infections of any grades or neutropenic fever (46.3%, 19/41) and one patient (4.2%) died of acute cerebral infarction within 6 weeks of treatment. Lower-dose decitabine demonstrated promising clinical response with acceptable toxicity profiles in patients with low- and intermediate 1-risk MDS. A higher response rate to decitabine was observed in patients with mutated genes. Therefore, lower-dose decitabine can be advocated for patients with low-risk MDS and mutated genes.
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http://dx.doi.org/10.7150/jca.56207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040893PMC
March 2021

Decitabine combined with low dose idarubicin and cytarabine (D-IA) followed by allo-HSCT improves acute myeloid leukemia and higher-risk myelodysplastic syndrome patient outcomes: results from a retrospective study.

Leuk Lymphoma 2021 Mar 7:1-18. Epub 2021 Mar 7.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, PR China.

Treatment for acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy is a major challenge for clinicians. We enrolled 154 patients ineligible for intensive chemotherapy who were prescribed D-IA regimen (decitabine 15-20 mg/m days 1 to 3-5, followed by idarubicin 3 mg/m for 5-7 days and cytarabine 30 mg/m for 7-14 days). For AML and MDS patients, the overall response rate after two cycles was 66.4% and 76.6%, respectively, and the 2-year overall survival rates were 29% and 31%, respectively. Fourteen (13.1%) AML and five (10.6%) MDS patients underwent allo-HSCT after complete remission. The allo-HSCT group survival time was significantly longer than the control group (median survival time not reached in HSCT group, 13 and 18.5 months in non-HSCT AML and MDS group). We concluded that D-IA regimen was effective and well tolerated for patients with AML or higher-risk MDS ineligible for intensive chemotherapy.
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http://dx.doi.org/10.1080/10428194.2021.1891230DOI Listing
March 2021

Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes.

Cancer Med 2021 03 20;10(5):1759-1771. Epub 2021 Feb 20.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Purpose: To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS).

Methods: A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS-related mutations sequencing.

Results: 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and <60 years old (p = 0.046). TP53 mutations were associated with complex karyotype (CK) (p < 0.001). DNMT3A mutations correlated with -Y (p = 0.01) whereas NRAS mutations correlated with 20q- (p = 0.04). The overall survival (OS) was significantly inferior in patients with +8 compared with those with normal karyotype (NK) (p = 0.003). However, the OS of sole +8 and +8 with one additional karyotypic abnormality was not different from NK (p = 0.16), but +8 with two or more abnormalities had a significantly shorter OS than +8 and +8 with one additional karyotypic abnormality (p = 0.02). In multivariable analysis, ≥60 years old, marrow blasts ≥5% and TP53 mutations were independent predictors for poor OS (p < 0.05), whereas SF3B1 mutations indicated better prognosis. Male IDH1 and IDH2 mutations and marrow blasts ≥5% were independent risk factors for worse leukemia free survival (LFS) (p < 0.05).

Conclusion: In this population of Chinese patients, trisomy 8 is the most common karyotypic abnormality. Patients with +8 showed a poorer OS compared with patients with NK. Sole +8 and +8 with one additional karyotypic abnormality had similar OS with NK, whereas +8 with two or more abnormalities had a significantly shorter OS. DNMT3A mutations correlated with -Y and NRAS mutations correlated with 20q-. TP53 mutations were associated with CK and had a poor OS. SF3B1 mutations indicated a favorable OS. IDH1 and IDH2 mutations independently indicated inferior LFS.
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http://dx.doi.org/10.1002/cam4.3786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940222PMC
March 2021

Mitochondrial genome of sing next-generation sequencing from China and its phylogenetic implication.

Mitochondrial DNA B Resour 2020 Jun 11;5(3):2432-2433. Epub 2020 Jun 11.

Guizhou Light Industry Technical College, Guiyang, P. R. China.

The complete mitochondrial genome (mitogenome) of (Diptera: Tephritidae: Dacinae) was sequenced and annotated. The mitochondrial genome is 15,273 bp (GenBank No. MT196006), containing 72.2% A + T (A 38.4%, C 16.9%, G 10.9%, and T 33.8%), which is the classical structure for insect mitogenome. All PCGs were started with ATN (ATA/ATG/ATT/ATC) and terminated with TAA except ND3, which ends with TAG. Additionally, the phylogenetic tree confirmed that was closely related to and . The current study would enrich the information about mitogenomes of the fruit flies.
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http://dx.doi.org/10.1080/23802359.2020.1775517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781919PMC
June 2020

Impact of mutational variant allele frequency on prognosis in myelodysplastic syndromes.

Am J Cancer Res 2020 1;10(12):4476-4487. Epub 2020 Dec 1.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, Zhejiang Province, P. R. China.

The clinical relevance of variant allele frequency (VAF) of recurrent mutations in myelodysplastic syndromes (MDS) has been increasingly reported. However, the prognostic value of mutational VAF across the genetic spectrum of MDS has not been extensively evaluated. In this study, we profiled the mutational spectrum of 382 newly diagnosed MDS patients using targeted next-generation sequencing. Exploratory analysis found that mutational VAF of some genes including , , and had significant associations with patient survival. Specifically, VAF ≥ 32% (HR 1.69, P = 0.025) and VAF ≥ 27% (HR 3.58, P < 0.001) were independently associated with shorter overall survival (OS). In contrast, VAF ≥ 15% had an independent association with better prognosis (HR 0.52, P = 0.048). In addition, high VAF was associated with an increased response to hypomethylating agents relative to low VAF (P = 0.009). Patients with high VAF more often possessed complex karyotypes than those with low VAF (P = 0.034). And patients with high VAF were more frequently classified as MDS with ring sideroblasts (MDS-RS) category than those with low VAF (P = 0.012). Meanwhile, we found that for some other genes like and , once their mutations appeared, it meant poor survival regardless of mutational VAF. These findings suggest that mutational VAF of certain genes should be considered into the routine prognostic prediction and risk stratification of MDS patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783761PMC
December 2020

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial.

Hematol Oncol 2020 Oct 24;38(4):531-540. Epub 2020 Jun 24.

Department of Hematology, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China.

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m daily, days 1 to 3; idarubicin, 6 mg/m daily, days 4 to 6; cytarabine 25 mg/m every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 μg/kg, from day 4 until neutrophil count increased to 1.0 × 10 /L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.
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http://dx.doi.org/10.1002/hon.2755DOI Listing
October 2020

TP53 mutations are associated with very complex karyotype and suggest poor prognosis in newly diagnosed myelodysplastic syndrome patients with monosomal karyotype.

Asia Pac J Clin Oncol 2020 Jun 7;16(3):172-179. Epub 2020 Feb 7.

Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Aim: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK).

Methods: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy-three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next-generation sequencing. Genetic and biological features and their association with survival were evaluated.

Results: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1-16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9-12.8) than those with non-vCK (16.1 months with 95% CI 11.5-20.8) (P = .02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5-11.5 vs 26.1 months with 95% CI 8.0-44.2, P < .01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild-type TP53 (60% vs 22.2%, P = .03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P = .03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS.

Conclusions: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors.
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http://dx.doi.org/10.1111/ajco.13316DOI Listing
June 2020

Mutation status and burden can improve prognostic prediction of patients with lower-risk myelodysplastic syndromes.

Cancer Sci 2020 Feb 24;111(2):580-591. Epub 2019 Dec 24.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129-4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144-8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662-14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848-16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR-MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDS and could help identify those with worse-than-expected prognosis for more aggressive treatment.
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http://dx.doi.org/10.1111/cas.14270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004535PMC
February 2020

Structural networks in children with autism spectrum disorder with regression: A graph theory study.

Behav Brain Res 2020 01 25;378:112262. Epub 2019 Sep 25.

Affiliated Brain Hospital to Nanjing Medical University, No. 264, Guangzhou Road, Gulou District, Nanjing City, Jiang Su Province, China. Electronic address:

Background: Regression is frequently described in Autism spectrum disorder (ASD). Limited comprehensive studies have been conducted in patients with ASD with regression.

Purpose: To explore the network topological properties in ASD children with (ASD-R) and without (ASD-NR) regression.

Methods: In this study, 29 ASD-R, 68 ASD-NR, and 40 children with developmental delay (DD) were recruited. We utilized graph theory to characterize the white matter structure networks by using diffusion tensor imaging and T1-weighted imaging on a 3-T magnetic resonance system. Statistical analyses were performed using IBM SPSS (version 23).

Results: ANCOVA showed significant differences in global efficiency, characteristic path length and sigma among the ASD-R, ASD-NR and DD groups, but the difference was not significant between the ASD-R and ASD-NR groups. There were 10 common hubs based on regional degree and regional efficiency in all groups. The hubness of the left superior frontal gyrus-dorsolateral, left middle occipital gyrus and right precuneus were enhanced (by regional degree) and that of the right thalamus was reduced (by regional efficiency) in the ASD-R relative to the ASD-NR group. After controlling for the course of regression, the CARS scores were significantly correlated with the regional efficiency of the right precuneus in the ASD-R group.

Conclusions: The ASD-R children were different from the ASD-NR children in the distribution of hub regions, although there were no global network property differences between them. In ASD-R children, the right precuneus (PCUN.R) might play an important role and relate to autism symptom severity.
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http://dx.doi.org/10.1016/j.bbr.2019.112262DOI Listing
January 2020

Decitabine improves overall survival in myelodysplastic syndromes-RAEB patients aged ≥60 years and has lower toxicities: Comparison with low-dose chemotherapy.

Blood Cells Mol Dis 2019 07 31;77:88-94. Epub 2019 Mar 31.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

Decitabine and low-dose chemotherapy are common treatments for intermediate and high risk myelodysplastic syndromes (MDS). In this study, we retrospectively assessed the efficacy and toxicity of the two regimens for MDS-refractory anemia with excess blasts (MDS-RAEB) patients. A total of 112 patients with a diagnosis of MDS-RAEB are included. The overall response (OR) and complete remission (CR) rate was comparable between the two groups (OR: 64.1% vs. 66.7%, p = 0.60; CR: 23.4% vs. 31.3%, p = 0.64). The OR rates of 20 mg/m/day and 15 mg/m/day decitabine regimen were comparable (69.0% vs. 60.0%, p = 0.46). Overall survival (OS) did not differ significantly between the groups (20.7 vs. 13.5 months, p = 0.17). In a subgroup analysis that included only patients at ≥60 years of age, survival benefit of decitabine was apparent (20.6 vs. 10.0 months, p = 0.03). In hematological toxicities, the lowest count of platelet in the decitabine group was higher significantly. And, the incidence of Grade 3-4 infection in the decitabine group was lower significantly. Our results demonstrate that both decitabine and low-dose chemotherapy are effective for MDS-RAEB, but decitabine was safer. Decitabine might be a better choice for patients at ≥60 years of age.
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http://dx.doi.org/10.1016/j.bcmd.2019.03.010DOI Listing
July 2019

Decitabine for myelodysplastic syndromes: dose comparison in a real world clinical setting.

Leuk Lymphoma 2019 07 8;60(7):1731-1739. Epub 2019 Jan 8.

a Department of Hematology, The First Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , Zhejiang , China.

We retrospectively studied 133 myelodysplastic syndrome patients receiving decitabine during January 2009 and September 2017. The dose of 15 mg/m/d ( = 83) and 20 mg/m/d ( = 50) had comparable overall response rates (ORR) (51.8% vs. 52.00%) and complete remission rate (CRR) (15.66% vs. 22.00%). The 15 mg/m/d group had a lower incidence of grade 3/4 neutropenia (60.24% vs. 88.00%,  < .05) and thrombocytopenia (65.06% vs. 88.00%,  < .05). The 15 mg/m/d group had a longer median overall survival (OS) (21.60 months vs. 15.23 months,  = .02). The same results were seen in refractory anemia with excess blasts (RAEB) patients: The 15 mg/m/d group also had comparable ORR, CRR, decreased hematological toxicities and longer OS. Further analysis suggested that survival benefit of 15 mg/m/d group was mainly in those patients with lower risk stratification. In conclusion, 15 mg/m/d decitabine is associated with a lower incidence of hematological toxicities and longer OS and may be more suitable for patients with relatively lower risk.
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http://dx.doi.org/10.1080/10428194.2018.1546853DOI Listing
July 2019

Analysis of clinical and molecular features of MDS patients with complex karyotype in China.

Blood Cells Mol Dis 2019 03 22;75:13-19. Epub 2018 Nov 22.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China. Electronic address:

We retrospectively analyzed 101 primary MDS patients with complex karyotype during January 2010 and April 2017.The median overall survival (OS) time was 13 (95% CI 9.98-16.02) months, and there was no significant difference in OS for different treatment. Chromosome 5/7 involvement was common (78.22%, 79/101) and associated with shorter OS (12 months vs. 28 months, P < 0.01) Monosomal karyotype (MK) is overlapped with CK in 79 patients, but was not statistically associated with shorter OS. While in 59 cases with genes sequenced, 57 (96.61%) patients were found to have at least one mutation of known significance, and TP53 was the most frequent (74.58%, 44/59), the median OS of patients with TP53 mutation was shorter than those without (10 vs. 27 months, P < 0.01). Multivariate analysis demonstrated that only TP53 mutation was the strongest independent prognostic factor for OS. Moreover, high variant allele frequency (VAF) of TP53 mutation (median VAF was 70.00%) was seen and associated with adverse survival (9 months vs. 13 months, p = 0.04). In conclusion, MDS patients with CK implied an unfavorable outcome regardless of any treatment, TP53 mutation occurs at a high frequency and has a higher VAF, both were associated with worse survival.
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http://dx.doi.org/10.1016/j.bcmd.2018.11.006DOI Listing
March 2019

Clinical and biological characteristics of acute myeloid leukemia with 20-29% blasts: a retrospective single-center study.

Leuk Lymphoma 2019 05 10;60(5):1136-1145. Epub 2018 Oct 10.

a Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou, Zhejiang , China.

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts should be considered AML or myelodysplastic syndromes (MDS). We retrospectively studied 382 patients, including 108 AML with 20-29% BM blasts (AML20-29), 210 AML with ≥30% BM blasts (AML ≥ 30), and 64 MDS with 10-19% BM blasts (MDS-EB2). We found that AML20-29 were more similar to MDS-EB2 in terms of advanced age, less blood count, the increased presence of poor-risk cytogenetics. The frequency of mutated genes in AML20-29 had both the characters of AML and MDS. Median overall survival of AML20-29 and MDS-EB2 were similar and shorter than those of AML ≥ 30 (p = .045). Multivariate analysis showed inferior survival with increased age, low platelet count and FLT3 mutations. Our findings suggest that AML20-29 have clinical features more similar to MDS than AML.
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http://dx.doi.org/10.1080/10428194.2018.1515938DOI Listing
May 2019

The high NRF2 expression confers chemotherapy resistance partly through up-regulated DUSP1 in myelodysplastic syndromes.

Haematologica 2019 03 27;104(3):485-496. Epub 2018 Sep 27.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

Although cytarabine has been widely considered as one of the chemotherapy drugs for high-risk myelodysplastic syndromes (MDS), the overall response rate is only approximately 20-30%. Nuclear factor erythroid 2-related factor 2 (NRF2, also called NFE2L2) has been shown to play a pivotal role in preventing cancer cells from being affected by chemotherapy. However, it is not yet known whether NRF2 can be used as a prognostic biomarker in MDS, or whether elevated NRF2 levels are associated with cytarabine resistance. Here, we found that NRF2 expression levels in bone marrow from high-risk patients exceeded that of low-risk MDS patients. Importantly, high NRF2 levels are correlated with inferior outcomes in MDS patients (n=137). Downregulation of NRF2 by the inhibitor Luteolin, or lentiviral shRNA knockdown, enhanced the chemotherapeutic efficacy of cytarabine, while MDS cells treated by NRF2 agonist Sulforaphane showed increased resistance to cytarabine. More importantly, pharmacological inhibition of NRF2 could sensitize primary high-risk MDS cells to cytarabine treatment. Mechanistically, downregulation of dual specificity protein phosphatase 1, an NRF2 direct target gene, could abrogate cytarabine resistance in NRF2 elevated MDS cells. Silencing NRF2 or dual specificity protein phosphatase 1 also significantly sensitized cytarabine treatment and inhibited tumors in MDS cells transplanted mouse models Our study suggests that targeting NRF2 in combination with conventional chemotherapy could pave the way for future therapy for high-risk MDS.
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http://dx.doi.org/10.3324/haematol.2018.197749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395322PMC
March 2019

Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis.

Anticancer Drugs 2018 10;29(9):904-910

Department of Oncology, the First Affiliated Hospital of Dalian Medical University.

The aim of the current study is to investigate programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions and to analyze the relationship between the expression of PD-L1 and PD-1 proteins and the molecular type, clinicopathological factors, and prognosis of invasive ductal carcinoma. We enrolled 136 patients with invasive ductal carcinoma of the breast. The expression of PD-L1 in tumor cells and that of PD-1 on paratumor-infiltrating immune cells was detected by immunohistochemistry, and the data were analyzed using SPSS software. The positive expression rates of PD-L1 and PD-1 in triple-negative breast cancer (TNBC) were 47.8 and 43.5%, which were higher than those of other subtypes (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 (P<0.05). The expression of PD-1 in the tumor-infiltrating immune cells was correlated with the expression of estrogen receptor, progesterone receptor, and Ki-67 and the histological grade (P<0.05). The expression of PD-L1 in tumor cells was correlated with the expression of PD-1 in paratumor-infiltrating immune cells (P<0.001). The expression of PD-L1 in tumor cells was found to be an independent prognostic risk factor with the progression-free survival rate for breast invasive ductal carcinoma (P=0.003). These results indicate that PD-L1 and PD-1 were highly expressed in TNBC which suggests that patients with TNBC may benefit from targeted immune therapies to a greater degree than patients with other subtypes. PD-L1 expression is an independent risk factor for breast invasive ductal carcinoma and expression of PD-L1 is expected to be a prognostic factor for breast cancer.
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http://dx.doi.org/10.1097/CAD.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143223PMC
October 2018

Absent Audiovisual Integration Elicited by Peripheral Stimuli in Parkinson's Disease.

Parkinsons Dis 2018 12;2018:1648017. Epub 2018 Apr 12.

Department of Neurology, Dokkyo Medical University, Tochigi 3210293, Japan.

The basal ganglia, which have been shown to be a significant multisensory hub, are disordered in Parkinson's disease (PD). This study was to investigate the audiovisual integration of peripheral stimuli in PD patients with/without sleep disturbances. Thirty-six age-matched normal controls (NC) and 30 PD patients were recruited for an auditory/visual discrimination experiment. The mean response times for each participant were analyzed using repeated measures ANOVA and race model. The results showed that the response to all stimuli was significantly delayed for PD compared to NC (all < 0.01). The response to audiovisual stimuli was significantly faster than that to unimodal stimuli in both NC and PD ( < 0.001). Additionally, audiovisual integration was absent in PD; however, it did occur in NC. Further analysis showed that there was no significant audiovisual integration in PD with/without cognitive impairment or in PD with/without sleep disturbances. Furthermore, audiovisual facilitation was not associated with Hoehn and Yahr stage, disease duration, or the presence of sleep disturbances (all > 0.05). The current results showed that audiovisual multisensory integration for peripheral stimuli is absent in PD regardless of sleep disturbances and further suggested the abnormal audiovisual integration might be a potential early manifestation of PD.
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http://dx.doi.org/10.1155/2018/1648017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924975PMC
April 2018

Isocitrate dehydrogenase 2 mutations correlate with leukemic transformation and are predicted by 2-hydroxyglutarate in myelodysplastic syndromes.

J Cancer Res Clin Oncol 2018 Jun 16;144(6):1037-1047. Epub 2018 Mar 16.

Department of Hematology, The First Affiliated Hospital, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.

Purpose: The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by the presence of somatically mutated hematopoietic stem cells (HSCs) that increase the risk of progression to secondary acute myeloid leukemia (sAML). Mutations in isocitrate dehydrogenase (IDH) are thought to correlate with the increased production of the oncogenic protein 2-hydroxyglutarate (2-HG) in AML. The aim of this study was to examine whether serum 2-HG has utility as a prognostic biomarker, and whether elevated 2-HG levels are predictive of IDH mutations in patients with MDS.

Methods: Genetic profiling was utilized to determine the genetic composition of a large cohort of MDS patients, including the presence or absence of IDH1 or IDH2 mutations (n = 281). Serum 2-HG levels were detected by liquid chromatography-tandem mass spectrometry.

Results: In the current study of MDS patients, elevated serum 2-HG levels were predictive of inferior overall- and leukemia-free survival irrespective of IPSS risk grouping. Higher serum 2-HG levels predicted the presence of IDH mutations. IDH2 patients had a higher risk of leukemic transformation. The co-occurrence of DNMT3A or SRSF2 mutations was found to be increased in IDH2 patients. IDH2 mutations were associated with significantly worse OS and LFS amongst patients with low-risk MDS by IPSS grouping.

Conclusions: The noted predictive value of serum 2-HG levels and IDH2 mutations on OS and LFS support the use of biomarkers and/or underlying cytogenetics in novel prognostic scoring systems for MDS.
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http://dx.doi.org/10.1007/s00432-018-2627-3DOI Listing
June 2018

Comparison for younger and older adults: Stimulus temporal asynchrony modulates audiovisual integration.

Int J Psychophysiol 2018 02 15;124:1-11. Epub 2017 Dec 15.

Cognitive Neuroscience Laboratory, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan; Intelligent Robotics Institute, Beijing Institute of Technology, Beijing 100081, China; Shenzhen Institute of Neuroscience, Shenzhen 518057, China. Electronic address:

Recent research has shown that the magnitudes of responses to multisensory information are highly dependent on the stimulus structure. The temporal proximity of multiple signal inputs is a critical determinant for cross-modal integration. Here, we investigated the influence that temporal asynchrony has on audiovisual integration in both younger and older adults using event-related potentials (ERP). Our results showed that in the simultaneous audiovisual condition, except for the earliest integration (80-110ms), which occurred in the occipital region for older adults was absent for younger adults, early integration was similar for the younger and older groups. Additionally, late integration was delayed in older adults (280-300ms) compared to younger adults (210-240ms). In audition‑leading vision conditions, the earliest integration (80-110ms) was absent in younger adults but did occur in older adults. Additionally, after increasing the temporal disparity from 50ms to 100ms, late integration was delayed in both younger (from 230 to 290ms to 280-300ms) and older (from 210 to 240ms to 280-300ms) adults. In the audition-lagging vision conditions, integration only occurred in the A100V condition for younger adults and in the A50V condition for older adults. The current results suggested that the audiovisual temporal integration pattern differed between the audition‑leading and audition-lagging vision conditions and further revealed the varying effect of temporal asynchrony on audiovisual integration in younger and older adults.
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http://dx.doi.org/10.1016/j.ijpsycho.2017.12.004DOI Listing
February 2018

Reduction of NANOG Mediates the Inhibitory Effect of Aspirin on Tumor Growth and Stemness in Colorectal Cancer.

Cell Physiol Biochem 2017 27;44(3):1051-1063. Epub 2017 Nov 27.

Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.

Background/aims: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear.

Methods: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons.

Results: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability.

Conclusion: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.
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http://dx.doi.org/10.1159/000485405DOI Listing
January 2018

Publisher Correction: PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.

Sci Rep 2017 11 7;7(1):15260. Epub 2017 Nov 7.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-017-14858-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677121PMC
November 2017

Altered patterns of resting-state functional connectivity between the caudate and other brain regions in medication-naïve children with attention deficit hyperactivity disorder.

Clin Imaging 2018 Jan - Feb;47:47-51. Epub 2017 Jul 28.

Institute of Children Health, Children's Hospital of Changzhou, Changzhou 213003, Jiangsu, China. Electronic address:

Background: Structural and functional alterations occur in the caudate of patients with attention-deficit/hyperactivity disorder (ADHD). Here we aimed to investigate the functional connectivity between the dorsal caudate and other brain regions in ADHD children.

Methods: Resting-state functional connectivity from 30 ADHD and 33 age- and gender-matched "normal" children were measured by functional Magnetic Resonance Imaging.

Results: Positive connectivity with dorsal caudate was observed in the prefrontal areas, cingulate cortex and temporal lobe. Negative functional connectivity was observed in the precuneus, occipital cortices and cerebellum. The connectivity of left dorsal caudate to left inferior frontal gyrus was correlated with severity of ADHD.

Conclusions: Connectivity of dorsal caudate with several brain regions was identified in ADHD children.
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http://dx.doi.org/10.1016/j.clinimag.2017.07.009DOI Listing
May 2018

MicroRNA-29a regulates lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophages through the Akt1/ NF-κB pathway.

Exp Cell Res 2017 11 12;360(2):74-80. Epub 2017 Aug 12.

First Affiliated Hosp Dalian Med Univ, Dept Oncol, Dalian 116011, PR China. Electronic address:

Akt activation in macrophages enhances lipopolysaccharide (LPS)-induced inflammatory responses through upregulation of the NF-κB signal pathway. Akt phosphorylation via microRNA (miR) caused the downregulation of Akt1. Here, we evaluated the role of miR-29a in LPS-triggered inflammatory responses. LPS stimulation of primary macrophages and RAW264.7 cells gradually increased the levels of miR-29a and was dependent on the LPS concentration. Overexpression of miR-29a in macrophages enhanced the expression of proinflammatory cytokines including IL-1β and IL-6, but not TNF-α. Conversely, knockdown of miR-29a diminished cytokine expression. Bioinformatics analyses indicated that Akt1 was a potential target of miR-29a through its interaction with the CDS region of Akt1. The miR-29a also enhanced LPS-induced NF-κB signaling through increased NF-κB transcriptional activity and phosphorylation of p65, and through binding to Akt1. Moreover, Akt1 silencing promoted the LPS-induced expression of IL-1β and IL-6, and upregulated the NF-κB pathway. Taken together, our results suggested that miR-29a participates in the regulation of inflammatory responses in LPS-stimulated macrophages by promoting NF-κB activation through targeting Akt1.
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http://dx.doi.org/10.1016/j.yexcr.2017.08.013DOI Listing
November 2017

PP2A inhibition from LB100 therapy enhances daunorubicin cytotoxicity in secondary acute myeloid leukemia via miR-181b-1 upregulation.

Sci Rep 2017 06 6;7(1):2894. Epub 2017 Jun 6.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.

Patients with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndromes have a poor prognosis marked by an increased resistance to chemotherapy. An urgent need exists for adjuvant treatments that can enhance or replace current therapeutic options. Here we show the potential of LB100, a small-molecule protein phosphatase 2 A (PP2A) inhibitor, as a monotherapy and chemosensitizing agent for sAML using an in-vitro and in-vivo approach. We demonstrate that LB100 decreases cell viability through caspase activation and G2/M cell-cycle arrest. LB100 enhances daunorubicin (DNR) cytotoxicity resulting in decreased xenograft volumes and improved overall survival. LB100 profoundly upregulates miR-181b-1, which we show directly binds to the 3' untranslated region of Bcl-2 mRNA leading to its translational inhibition. MiR-181b-1 ectopic overexpression further diminishes Bcl-2 expression leading to suppression of sAML cell growth, and enhancement of DNR cytotoxicity. Our research highlights the therapeutic potential of LB100, and provides new insights into the mechanism of LB100 chemosensitization.
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http://dx.doi.org/10.1038/s41598-017-03058-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460144PMC
June 2017

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone.

J Cancer Res Clin Oncol 2017 May 20;143(5):873-882. Epub 2017 Jan 20.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.

Purpose: The aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes-refractory anemia with excess of blasts (MDS-RAEB).

Methods: The current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.

Results: A total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2-21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7-38.1 vs. 14.7 months with 95% CI of 11.4-18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1-29.7 vs. 11.9 months with 95% CI of 4.0-19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4-49.2 vs. 17.8 months with 95% CI of 13.8-21.8 months in the chemotherapy group, p = 0.039). Grade 3-4 hematological and non-hematological toxicities were not significantly different between the two groups.

Conclusions: Decitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.
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http://dx.doi.org/10.1007/s00432-016-2331-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384967PMC
May 2017

Successful treatment of osteomyelitis with Micafungin in a leukemia patient.

IDCases 2016 9;6:109-111. Epub 2016 Nov 9.

Hematology Department, the First Affiliated Hospital of Zhejiang University, China.

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http://dx.doi.org/10.1016/j.idcr.2016.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142103PMC
November 2016

Diagnosis and management of acquired thrombotic thrombocytopenic purpura in southeast China: a single center experience of 60 cases.

Front Med 2016 Dec 23;10(4):430-436. Epub 2016 Dec 23.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 (range, 17 to 78) years with a female predominance (male:female ratio, 1:1.60). ADAMTS 13 activity were analyzed in 43 patients, among whom 33 (76.7%) patients had a baseline level of < 5%. Mortality was 30%. Plasma exchange (PEX) was performed in 62 of 69 (89.9%) episodes. Corticosteroids were administered in 54 of 69 (78.3%) episodes. Other immunosuppressants (e.g., vincristine, cyclosporine, and cyclosporin) were used in 7 of 69 (10.1%) episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.
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http://dx.doi.org/10.1007/s11684-016-0492-5DOI Listing
December 2016

Diffuse large B-cell lymphoma in colon confounded by prior history of colorectal cancer: A case report and literature review.

Oncol Lett 2016 Feb 7;11(2):1493-1495. Epub 2016 Jan 7.

Department of Hematology, The First Affiliated Hospital of Zhejiang University, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.

A 66-year-old male underwent left hemicolectomy for rectal adenocarcinoma in 2008. Five years later he was admitted to hospital with abdominal pain. A computed tomography scan revealed notable thickening of the middle of the ascending colon wall, and colonoscopy revealed an ulcerofungating mass of 3×3 cm in the cecum and extending to the ascending colon. Under the consideration of cancer recurrence, laparoscopic right hemicolectomy was performed directly. Surgical specimens revealed sheets of large pleomorphic lymphoid cells with nuclei of different sizes, nucleoli and mitotic phases visible in most cells. These tested positive for CD45, CD20 and CD79a diffusely, but negative for CD3, CD5, Bcl-2, Bcl-6 and ALK. The Ki-67 proliferation index was 40%. Epstein-Barr virus hybridization did not reveal any positive signals in any of the tumor cells. Based on these findings, the recurrent tumor was diagnosed as diffuse large B-cell lymphoma. The patient could have avoided surgery and received chemotherapy only; however, the case was confounded by the patient's prior history of colorectal cancer due to the rarity of colon lymphoma following rectal cancer in the same patient. It is therefore essential to investigate carefully and differentiate between potential lesions during routine postoperative colonoscopy following colorectal cancer surgery, as patients may present with rare colon lymphoma, which may be confused with a recurrence of colorectal cancer.
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http://dx.doi.org/10.3892/ol.2016.4078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734296PMC
February 2016

[Analysis of the karyotype abnormalities and its prognostic in 298 patients with myelodysplastic syndrome].

Zhonghua Xue Ye Xue Za Zhi 2015 Apr;36(4):297-301

MDS Center, 1st Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou 310003, China.

Objective: To investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS).

Methods: 298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted.

Results: The WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (P<0. 05). An analysis based on IPSS-R Scoring System showed that advanced risk stratification (except the low-risk group) gradually enhanced the incidence of karyotypic abnormalities (P<0.05). In addition, the probability of evolution to leukemia increased with the higher IPSS-R score (P<0.05). In RAEB group, the cases with +8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes.

Conclusion: Karyotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.
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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2015.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342621PMC
April 2015
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