Publications by authors named "Xinping Zhou"

28 Publications

  • Page 1 of 1

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

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

Many-body near-field radiative heat transfer: methods, functionalities and applications.

Rep Prog Phys 2021 Feb 10. Epub 2021 Feb 10.

Huazhong University of Science and Technology, Wuhan, 430074, CHINA.

Near-field radiative heat transfer (NFRHT) governed by evanescent waves, provides a platform to thoroughly understand the transport behavior of nonradiative photons, and also has great potential in high-efficiency energy harvesting and thermal management at the nanoscale. There have been numerous and impactful progresses of theories and experiments in terms of NFRHT in two-body systems. However, it is more usual in nature that objects participate in heat transfer process in many-body form rather than the frequently-considered two-body scenarios, and the inborn mutual interactions among objects are important to be understood and utilized for practical applications. Therefore, the issue of many-body NFRHT on aspects of theories and applications becomes increasingly explored. The last decade has witnessed considerable achievements on many-body NFRHT, ranging from the establishment of different calculation methods to various unprecedented heat transport phenomena that are distinct from two-body systems. In this invited Review, we introduce concisely the basic physics of NFRHT, lay out various theoretical methods to deal with many-body NFRHT, and highlight unique functionalities realized in many-body systems and the resulting applications. At last, the key challenges and opportunities of many-body NFRHT in terms of fundamental physics, experimental validations, and potential applications are outlined and discussed.
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http://dx.doi.org/10.1088/1361-6633/abe52bDOI Listing
February 2021

Real-world data of chronic myelomonocytic leukemia: A chinese single-center retrospective study.

Cancer Med 2021 03 8;10(5):1715-1725. Epub 2021 Feb 8.

Myelodysplastic Syndrome Center, Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Chronic myelomonocytic leukemia (CMML) is a rare disease of elderly people characterized by the presence of sustained peripheral blood monocytosis, overlapping features of myeloproliferation, and myelodysplasia. We present a large retrospective study of 156 CMML patients in China. Mean age at diagnosis was 68 years old (range 23-91). According to the CMML-specific prognostic scoring system (CPSS), 10 patients (8.3%) were low risk, 27 patients (22.5%) were intermediate-1 risk, 72 patients (60%) were intermediate-2 risk, and 11 patients (9.2%) were high risk. A total of 90 patients (57.7%) received hypomethylating agents (HMAs) treatment, 19 patients (12.2%) received chemotherapy and 47 patients (30.1%) received the best supportive care. Seventeen patients (10.9%) underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) after HMAs treatment or chemotherapy. With a median follow-up of 35.3 months, overall response rate (ORR) was 69.5% in the HMAs ± chemotherapy group, 79.5% in the HMAs monotherapy group, 60.0% in the HMAs + chemotherapy group, and 37.5% in the chemotherapy group. HMAs monotherapy group had prolonged OS compared with the chemotherapy group (23.57 months vs. 11.73 months; p = 0.035). Patients who achieved ORR had prolonged OS (25.83 months vs. 8.00 months; p < 0.001) and LFS (20.53 months vs. 6.80 months; p < 0.001) compared with those not achieved ORR in the HMA ± chemotherapy group. By univariate analysis, only higher hemoglobulin (≥80 g/L) and lower serum LDH levels (<300 U/L) predicted for better OS and LFS. By multivariate analysis, only Hb ≥ 80 g/L predicted for prolonged OS, Hb ≥ 80 g/L, and monocytes < 3 × 109/L predicted for prolonged LFS. In summary, our study highlights the benefit of HMAs therapy in CMML, but we still need to develop novel therapeutics to achieve better outcomes.
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http://dx.doi.org/10.1002/cam4.3774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940209PMC
March 2021

Unraveling of the Aroma-Active Compounds in Virgin Camellia Oil ( Abel) Using Gas Chromatography-Mass Spectrometry-Olfactometry, Aroma Recombination, and Omission Studies.

J Agric Food Chem 2021 Feb 1. Epub 2021 Feb 1.

Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Key Laboratory of Oilseeds Processing of Ministry of Agriculture, Hubei Key Laboratory of Lipid Chemistry and Nutrition, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Wuhan, Hubei 430062, People's Republic of China.

Camellia oil is a popular edible oil in China as a result of its nutritional properties. However, the key odorants of camellia oil remain unclear. In this study, the volatiles of virgin camellia oil (VCO) were extracted by solvent-assisted and non-solvent-assisted methods. A total of 66 volatile compounds were identified using gas chromatography-mass spectrometry-olfactometry, with flavor dilution factors ranging from 1 to 729 via aroma extraction dilution analysis. Among them, 10 odorants were identified for the first time in VCO. Moreover, 41 volatiles were confirmed as aroma-active compounds with odor activity values greater than 1. Aroma recombination and omission studies demonstrated that aldehydes, esters, acids, and heterocyclic compounds significantly contribute to the aroma profiles of VCO. Hexanal, octanal, (,)-2,4-heptadienal, (,)-2,4-nonadienal, decyl acetate, ethyl benzoate, ethyl 2-methylbutanoate, 2-methylbutyl ()-2-methyl-2-butenoate, 2-methylbutanoic acid, hexanoic acid, 2-pentylfuran, and 2-methyl-3-furanthiol could impart roasted-like, nut-like, fat-like, fruit-like, grass-like, and sweat-like odors and were the key odorants in VCO. The lipoxygenase pathway was possibly responsible for the formation of key odorants in VCO. This work provides an extract aroma consistent for virgin camellia oil.
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http://dx.doi.org/10.1021/acs.jafc.0c07321DOI Listing
February 2021

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

Application of Rare-Earth Elements and Comparison to Molecular Markers in Oil-Source Correlation of Tight Oil: A Case Study of Chang 7 of the Upper Triassic Yanchang Formation in Longdong Area, Ordos Basin, China.

ACS Omega 2020 Sep 27;5(35):22140-22156. Epub 2020 Aug 27.

Key Laboratory of Petroleum Resources, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, 382 Donggang West Road, Lanzhou 730000, Gansu Province, China.

The biomarker features of 10 Chang 7 crude oil samples were investigated by gas chromatography-mass spectrometry (GC-MS), and the rare-earth element (REE) compositions of 16 Chang 7 and Chang 8 crude oil samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS) for the first time in Longdong area. Oil-source correlation analysis was improved by biomarkers and REEs. The distribution and relative ratios of a series of biomarker parameters in saturated hydrocarbons and aromatic hydrocarbons of crude oil samples indicate that Chang 7 tight oil has already reached the mature stage. The organic matter mainly comes from lower aquatic organisms of algae, with some contribution of micro-organisms and bacteria, while the forming environment of tight oil is mainly the transitional environment of sub-oxidizing to sub-reducing. The V/(V + Ni) and Ni/Co ratios of crude oil samples suggest that the specific redox conditions of Chang 7 and Chang 7 samples were slightly oxic, while Chang 7 and Chang 8 samples were formed under an anoxic environment. The results of both biomarker-based and REE-based oil-source correlation analysis indicate that Chang 7 and Chang 7 tight oils come from Chang 7 mudstone, while most of the Chang 7 tight oils are from Chang 7 oil shale, with part of mixed from Chang 7 mudstone. This recognition may indicate that Chang 7 mudstone and oil shale are two relatively independent hydrocarbon self-generation and near-storage systems. The analysis results demonstrate that the REE composition in crude oil is an efficient and accurate tool for oil-source correlation in the petroleum system.
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http://dx.doi.org/10.1021/acsomega.0c02233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482083PMC
September 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

Synthesis and biological evaluation of calycanthaceous alkaloid analogs.

Bioorg Med Chem 2019 11 5;27(21):115088. Epub 2019 Sep 5.

Key Laboratory of Botanical Pesticide R & D in Shaanxi Province, Yangling 712100, Shaanxi, China. Electronic address:

Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81 µg mL, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63 µg mL. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1 ng mL, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4 Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
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http://dx.doi.org/10.1016/j.bmc.2019.115088DOI Listing
November 2019

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

The relation of SF3B1 mutation and intracellular iron in myelodysplastic syndrome with less than 5% bone marrow blasts.

Leuk Lymphoma 2019 05 9;60(5):1179-1186. Epub 2018 Nov 9.

a MDS Center, Department of Hematology, the First Affiliated Hospital, College of Medicine , Zhejiang University , Hangzhou , China.

According to 2008 WHO classification RARS is regarded as less than 5% blasts and more than 15% ring sideroblasts in the bone marrow. In 2016 WHO classification MDS-RS is revised as more than 15% ring sideroblasts or more than 5% ring sideroblasts in the presence of the SF3B1 mutation. In our study, we classified intracellular iron in bone marrow into four types according to the size and quantity of iron granules. We found that there was a significant difference between SF3B1-mutant and SF3B1-wild-type MDS patients in intracellular iron III, intracellular iron IV and ring sideroblasts. We defined intracellular iron (III + IV + RS)%×100 as 'Iron score'. We suggest that the patients carrying SF3B1 mutation with Iron score ≥10 will extend the subtype of MDS-RS, in addition to the current WHO classification criteria. This study gives us a new insight into the relation of SF3B1 mutation and intracellular iron in lower-risk MDS.
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http://dx.doi.org/10.1080/10428194.2018.1520990DOI Listing
May 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

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

In vitro immunological and anti-complementary activities of two water-soluble lignins from Zizyphus jujube cv. Jinchangzao.

Int J Biol Macromol 2017 Dec 8;105(Pt 1):204-212. Epub 2017 Jul 8.

Xinjiang Production & Construction Corps Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin, Tarim University, Alar, 843300, China; Engineering Laboratory of Chemical Resources Utilization in South Xinjiang of Xinjiang Production & Construction Corps, Tarim University, Alar, 843300, China. Electronic address:

Two homogenous biological macromolecules, designated as JJC1 and JJC2 were extracted from Zizyphus jujube cv. Jinchangzao. Their molecular weights were determined to be 56.03 and 112.11kDa by high performance gel permeation chromatography (HPGPC), respectively. Chemical and spectral analysis indicated that both JJC1 and JJC2 mainly consisted of lignin, along with carbohydrates (∼18%). Both JJC1 and JJC2 could stimulate the proliferation of spleen lymphocytes, and enhance phagocytosis and NO production of RAW264.7 cells. In addition, JJC2, but not JJC1 elicited an inhibitory effect on complement activation through the classical pathway (CH: 2.73mg/mL) as well as the alternative pathway (AP: 2.99mg/mL). These findings implied that water-soluble lignins were one of the bioactive components in Z. jujube, and further provided insights into the understanding of molecular basis for diverse medicinal and nutritional values of this fruit.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.07.026DOI Listing
December 2017

Salvage therapy with lenalidomide containing regimen for relapsed/refractory Castleman disease: a report of three cases.

Front Med 2017 Jun 3;11(2):287-292. Epub 2017 Apr 3.

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

Castleman disease (CD) is uncommon non-clonal lymphoproliferative disorder with unknown etiology. No standard therapy is recommended for relapsed/refractory CD patients, thus requiring development of novel experimental approaches. Our cohort of three adult patients with multicentric CD (MCD) were treated with refractory to traditional chemotherapy lenalidomide-containing regimens (10-25 mg lenalidomide perorally administered on days 1-21 in 28-day cycle) as second- to fourth-line treatment. Partial remission was achieved in first plasma-cell CD patient, who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy. Partial remission was obtained in second patient with CD and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Third case showed complete remission with complete disappearance of pleural effusion and ascites and normalization of platelet count. To conclude, encouraging clinical responses were achieved in cohort of three patients with lenalidomide-based regimen, though long-term efficacy remains to be observed.We propose further investigation of therapeutic potential of this drug in treating MCD.
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http://dx.doi.org/10.1007/s11684-017-0510-2DOI Listing
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

Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives.

Molecules 2016 Sep 9;21(9). Epub 2016 Sep 9.

Key Laboratory of Protection & Utilization of Biological Resources in Tarim Basin of Xinjiang Production and Construction Corps/College of Life Sciences, Tarim University, Alar 843300, Xinjiang, China.

A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R₄ and R₅ significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents.
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http://dx.doi.org/10.3390/molecules21091207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273825PMC
September 2016

[Clinical and cytogenetic study of chromosome 1 abnormality in myelodysplastic syndrome].

Zhonghua Xue Ye Xue Za Zhi 2015 Oct;36(10):818-23

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

Objective: To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome(MDS)to couple its association with clinical presentation and prognosis.

Methods: R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.

Results: Of 672 cases of patients with MDS, chromosome 1 aberration[der(1), dup(1), -1 were most frequent] were found in 41(6.1%)cases. 1q trisomy was found in 18/41(43.9%)cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18(0.56-54.28)months. Median survival of 36 cases after 2010 was 17.48(95% CI 14.38-20.58)months. There were significant differences on median survival between RAEB and non-RAEB groups(χ²=10.398, P=0.001), and between with more than 3 chromosome abnormalities and with less than 3 groups(χ²=3.939, P=0.047). RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

Conclusion: Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.
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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2015.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364937PMC
October 2015

[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

Ghrelin prevents neuronal apoptosis and cognitive impairments in sepsis-associated encephalopathy.

Neuroreport 2011 Dec;22(18):959-64

Department of Surgical Intensive Care Unit, the First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, People's Republic of China.

The present study explored the effect of ghrelin in protecting neurons from apoptosis in sepsis-associated encephalopathy. Ghrelin (100 nM) increased the cell viability treated with lipopolysaccharide (1.0 μg/ml, 24 h). The expression of p-Akt and Bcl-2 were decreased and caspase-3 increased both in lipopolysaccharide-treated primary hippocampal cultures and in the cecal ligation and perforation model, which were alleviated in the presence of ghrelin. In vitro, the protecting effect of ghrelin was almost abolished by the Akt inhibitor, SH-5. In vivo, the cecal ligation and perforation rats exhibited emotional, learning, and memory deficits. Administration of ghrelin attenuated the cognitive deficits significantly. These results indicate that ghrelin alleviates neuronal apoptosis and subsequent cognitive impairments in sepsis-associated encephalopathy through the Akt pathway.
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http://dx.doi.org/10.1097/WNR.0b013e32834d38ceDOI Listing
December 2011
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