Characteristics of a patient with myeloid neoplasm and co-existence of t(7;11)(p15;p15) and t(5;12)(q33;p13) translocations / 中华医学遗传学杂志

OBJECTIVE@#To delineate the clinical and molecular characteristics of a patient with myeloid neoplasm and co-existence of t(7;11)(p15;p15) and t(5;12)(q33;p13) translocations.@*METHODS@#Clinical data of the patient was collected. Conventional karyotyping, reverse transcriptase (RT)-PCR and next generation sequencing (NGS) were carried out to delineate its genetic features.@*RESULTS@#The patient has featured recurrent rash, fatigue, loss of appetite and splenomegaly. Laboratory test suggested hyperleukocytosis of FAB-M2-subtype. Neither eosinophilia nor basophilia was presented. NUP98/HOXA9 and ETV6/PDGFRB fusion genes were detected by RT-PCR. NGS and DNA-PCR showed the co-existence of WT1 p.C423Y, KRAS p.G12D and DNMT3A p.R882C mutations. The patient achieved morphological remission after imatinib plus coventional chemotherapy (standard IAC regimen). However, the disease has relapsed shortly after. Treatment was switched to HHT-Ara-C-Acla regimen, no hematological response was observed. The ETV6/PDGFRB fusion gene was undetectable in bone marrow sample, though strong expression of NUP98/HOXA9 was detectable throughout the whole course.@*CONCLUSION@#Acute myeloid leukemia in association with the co-existence of NUP98/HOXA9 and ETV6/PDGFRB fusion genes have unique clinical and genetic features. Imatinib seems to have no impact on the overall survival in such cases.

A multivariate model for predicting induction response and prognosis in core binding factor acute myeloid leukemia / 中华内科杂志

Objective@#To evaluate the efficacy and prognostic factors in core binding factor (CBF) acute myeloid leukemia (AML) under current therapy modalities, therefore optimizing the treatment strategies.@*Methods@#Standard cytological and immune methods including next generation sequencing (NGS) were used for risk stratification. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were assessed by multivariate Logistic and Cox regression models in a total of 206 adults (aged 16-65 years) with CBF-AML, including 152 AML patients with t(8;21) and 54 with inv(16).@*Results@#The CR rate of inv(16) patients after first course was 54/54(100%), significantly higher than that of t(8;21) patients [127/147(86.4%), P=0.005]. The fusion transcript level and KIT mutation were independent factors related to CR rate in t(8;21) patients (P=0.044 and 0.027; respectively). DFS and OS in inv(16) patients tended to be more superior than that in t(8;21) patients (P=0.066 for DFS; P=0.306 for OS; respectively). Multivariate Cox identified negative expression of CD19 and female gender the independent predictors of inferior DFS in t(8;21) patients (P=0.000 for CD19; P=0.006 for sex; respectively). Analysis of combining CD19 with gender indicated that females/CD19-subpopulation had significantly poor DFS than did males/CD19+ ones (Bonferroni-P<0.000 01). The number of mutations in each patient, FLT3-ITD and additional karyotype abnormalities did not affect CR rate and DFS (all P>0.05).@*Conclusions@#Patients with inv(16) have better induction response than those with t(8;21). High level of fusion transcripts and positive KIT mutation are associated with low CR rate in t(8;21) patients. Negative CD19 expression and female gender are independent predictors of inferior DFS in t(8;21) patients.

Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells / 中华血液学杂志

Objective@#To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro.@*Methods@#Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1.@*Results@#BGJ398 effectively inhibited cell proliferation by dose-dependent manners. BGJ398(1.4 µmol/L) induced apoptosis of KG-1 cells by 36.4%, compared with 4.5% in the control group(P<0.001). Treatment with BGJ398 at 1.4 µmol/L led to significant increases in the expression levels of caspase-3, and decreases in the expression of Bcl-2 (P<0.005). In accordance with these results, Western blot analysis further confirmed the increased expression of Bcl-2 protein along with elevated caspase-3 activity. In addition, BGJ398 markedly down-regulated FGFR1OP2-FGFR1 fusion protein, p-AKT and p-S6K expression, but not p-ERK expression.@*Conclusion@#Novel pan-FGFR inhibitor BGJ398 substantially suppressed KG-1 cell growth and induced apoptosis by inhibiting the expression of FGFR1, p-AKT, p-S6K and regulating apoptosis-related proteins.

A study on the current situation of human resource and demand of pharmaceutical companies in Heilongjiang Province / 中华地方病学杂志

Objective The study was focused on the current situation of human resources of pharmaceutical enterprises in Heilongjiang Province, to solve the problems of workforce shortage in small- and medium-sized pharmaceutical enterprises, and put forward corresponding countermeasures. Methods A convenient sampling method was used to investigate the basic situation of 12 pharmaceutical enterprises in Heilongjiang Province in June - November 2016, and interviews and questionnaire survey were conducted with the employees of human resources departments. The basic situation of the survey included: the general situation, the demand for talent, the development of pharmaceutical enterprises and so on. Staff interviews included: the number of talents introduced and the number of outflows in the past 3 years, human resources needs, knowledge and ability of pharmaceutical enterprises. The staff survey included: employee job satisfaction, turnover tendency and career development prospects. Results The number of employees in the 12 pharmaceutical enterprises was 22065. Employees' age was in 34 - < 44 years old, with low education qualifications, 74.6% (16456/22065) of employees attended junior college or below . There were 6246 technical personnel , most of them (3678) received college education. In the interviews with 36 employees, it was found that the pharmaceutical enterprises were short of workforce. The unstable sources for the workforce and brain drain were the biggest problem in the development of pharmaceutical enterprises. In the 591 questionnaires, 24.6%(145/591) of employees had the idea of changing jobs in the past year. Conclusion Pharmaceutical enterprises should pay attention to the introduction and training of talented staff, and develop a series of preferential conditions to attract them, so as to achieve the goal of thriving enterprises by talented workforce.

HPLC fingerprint of Xuanbo Shuangsheng Granule / 复旦学报（医学版）

Objective To establish the HPLC fingerprint of Xuanbo Shuangsheng Granule for its quality control.Methods The components were separated on an Agilent TC-C18 column (150 mm ×4.6 mm,5 μm) at 25 ℃,with a gradient elution in 0-60 min at the flow rate of 1 mL/min using 0.2％ acetic acid aqueous solution and methanol as the mobile phase.The detection wavelength was 278 nm.By detecting 11 batches of Xuanbo Shuangsheng Granule,the HPLC fingerprint was established using Similarity Evaluation System for Chromatographic Fingerprint of TCMs (Version 2004A)and the common peaks were analyzed and identified in raw herbal material.Results The HPLC fingerprint of Xuanbo Shuangsheng Granule was obtained with similarity all over 0.9.Totally 27 common peaks were confirmed,and each common peak could be found in raw herbal medicines.Based on the reference substances,5 common peaks were identified,including phellodendrine (peak 11),liquiritin (peak 22),angoroside C (peak 25),cinnamic acid (peak 26) and harpagoside (peak 27).Conclusions This method is simple,accurate,repeatable and reliable,which could be applied in the quality control of Xuanbo Shuangsheng Granule.

Correlation of cytogenetic changes with VEGF and TRacp-5b levels among 60 elderly patients with multiple myeloma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the correlation of cytogenetic changes with serum vascular endothelial growth factor (VEGF) and serum tartrate resistant acid phosphatase (TRacp-5b) levels among elderly patients with multiple myeloma (MM).</p><p><b>METHODS</b>Chromosomal changes were analyzed with a modified culturing method in the presence of IL-6. Serum levels of VEGF and TRacp-5b were determined with enzyme-linked immunosorbent assays (ELISA).</p><p><b>RESULTS</b>Among the 60 MM patients, chromosomal abnormalities were found in 27 cases, including 22 with numerical abnormalities and 15 with structural abnormalities. Many patients had both numerical and structural abnormalities. For 33 patients with a normal karyotype, the levels of VEGF and TRacp-5b were 117.35 ± 55.26 pg/mL and 4.15 ± 2.15 U/L, respectively, while for 27 patients with an abnormal karyotype, the levels of VEGF and TRacp-5b were 190.26 ± 85.74 pg/ml and 5.96 ± 2.24 U/L, respectively. The difference between the two groups was significant (P<0.05).</p><p><b>CONCLUSION</b>Compared with MM patients with a normal karyotype, the levels of VEGF and TRacp-5b are higher in those with cytogenetic abnormalities.</p>

Study of NK cells dysfunction in multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3-CD56+NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme- linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry.</p><p><b>RESULTS</b>There are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5 ± 6.5) % vs (25.4 ± 5.9)%, P=0.044］.</p><p><b>CONCLUSION</b>The higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.</p>

8p11 myeloproliferative syndrome with CEP110-FGFR1 fusion in a patient / 中华医学遗传学杂志

OBJECTIVE To explore the clinical and laboratory features of a patient with 8p11 myeloproliferative syndrome (EMS) and CEP110-FGFR1 fusion. METHODS Combined bone marrow cytology, fluorescence in situ hybridization, fusion gene detection was used to analyze the patient. RESULTS Clinically, the patient had many features similar to those with chronic myelomonocytic leukemia, which included hyperleukocytosis, marked eosinophilia, monocytosis, myeloid hyperplasia and hyperplasia. Fluorescence in situ hybridization analysis for FGFR1 gene rearrangement was positive. Further study of the mRNA also confirmed an in-frame fusion between exon 38 of the CEP110 gene and exon 9 of FGFR1 gene. CONCLUSION EMS with CEP110-FGFR1 fusion is a very rare and distinct myeloproliferative neoplasm. FISH and molecular studies may improve its diagnosis.

CALR gene mutation detection and clinical observation of 150 essential thrombocythemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the prevalence of CARL gene mutations and the mutation types in patients with essential thrombocythemia (ET), and to compare the patients clinical characteristics of CALR mutation with JAK2 V617F, MPL W515K mutation patients and triple negative group.</p><p><b>METHODS</b>The mutations of CALR gene at extron 9 and MPL W515K in 150 ET patients were detected by PCR amplification followed by direct sequencing of genomic DNA, the JAK2 V617F mutation by using allele specific PCR.</p><p><b>RESULTS</b>(1)The CALR mutations were found in 38 patients (25.3%) of 150 ET patients. A total of 4 types of CALR mutations were identified (type Ic.1092_1143del52bp, n=17; type II c.1154_1155insTTGTC, n=16; type III c.1094_1139del46bp, n=4; type IV c.1103_1136del34bp, n=1). (2)The incidence of JAK2 V617F and MPL W515K was 61.3% (92/150) and 2.7% (4/150), respectively. The frequency of CALR mutation was 70.4% (38/54) in 54 ET patients without JAK2 V617F and MPL W515K mutations. The co-occurrence of any two kinds of gene mutations was not detected. (3)The hemoglobin level and leukocyte counts of patients with CARL mutations were significantly lower than that in patients with JAK2 V617F mutations (P<0.05). The median age of patients with CALR mutation was significantly higher than that of triple negative patients (59 years vs 29.5 years, P<0.01). Cytogenetic analysis was performed in 147 patients, and there were 4 abnormal karyotype cases. CALR mutation incidence was significantly higher in abnormal karyotype cases than that in normal ones (75% vs 24.5%, P=0.019).</p><p><b>CONCLUSION</b>The incidence of CALR mutations is high in ET patients without JAK2 V617F and MPL W515K mutations, and is associated with abnormal karyotype. CARL-mutated cases showed a significantly lower leucocyte and hemoglobin levels compared with JAK2 V617F mutated cases.</p>

Ontology and associated data-based library resources integration model / 中华医学图书情报杂志

After the application of associated data in digital library and in library resources integration was described, the necessity of library resources integration was analyzed, the semantic association process of library resources and the problems of library resources in research on semantic association were studied in terms of system construction, technical implementation and discovery algorithm. The semantic integration of library resources was achieved by de-signing the integration framework, ontology and associated data.

Biocompatibility of carboxymethyl chitosan membranes with human skin melanocytes / 中华皮肤科杂志

Objective To study the biocompatibility of carboxymethyl chitosan (CMCS) membrane with melanocytes from healthy human skin,and to investigate the feasibility to transport and carry melanocytes by using CMCS membrane.Methods CMCS membrane was prepared by a casting method combined with a glutaraldehydebased cross-linking method.Melanocytes were isolated from the foreskin of healthy men,and subjected to primary culture and subculture.The third-passage melanocytes were classified into two groups to be cultured on the CMCS membrane (test group) or traditional culture plates (control group).Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate the proliferative activity of melanocytes,and a sodium hydroxide-based lysis method to determine melanin content.HMB45 staining was conducted,and tyrosinase activity was estimated for melanocytes.Results Inverted microscopy showed that melanocytes were evenly distributed on the CMCS membrane with a normal shape.The melanocytes adherent to the CMCS membrane stained positive for anti-HMB45 monoclonal antibody.The growth curve of the melanocytes on the CMCS membrane,which was obtained from MTT assay,demonstrated that CMCS membrane could support the normal growth of melanocytes.No significant difference was observed between the test group and control group in melanin content (0.083 ± 0.015 vs.0.066 ± 0.008,t =2.38,P ＞ 0.01) or tyrosinase activity (0.234 ± 0.083 vs.0.241 ± 0.061,t =0.23,P ＞ 0.05).Conclusion CMCS membrane can maintain the normal biological activity of melanocytes and have good biocompatibility with skin melanocytes.

Establishment of digital resource performance assessment system and scientific allocation of digital re-sources in academic library / 中华医学图书情报杂志

The effective and fair allocation model of digital resources was studied by establishing the acquisition performance assessment system and mechanism.The optimal allocation program of digital resources was proposed according to the digital resource performance assessment in Library of Mudanjiang Medical College for the reference of academic library in its scientific allocation of digital resources.

Expression and significance of tumor suppressor gene Kruppel-like transcription factor 6 mRNA and protein in gastric cancer / 肿瘤研究与临床

Objective To investigate the correlation between Kruppel-like transcription factor 6 (KLF6) and gastric cancer.Methods By using immunohistochemistry (IHC) and reverse transcription PCR,the expression of KLF6 protein and mRNA in human gastric carcinoma specimens and adjacent tissues from 73 patients were examined.Results The KLF6 protein expression rates were 39.7 ％ (29/73) and 90.41％(66/73) in 73 cases of gastric cancer and adjacent tissues,The KLF6 protein expression was significantly lower in human gastric carcinomas than the adjacent tissues by chi-square test (P ＜ 0.01).The KLF6 expression rates were 25.0 ％ (10/40),57.6 ％ (19/33) in poorly and well differentiated cancer.The difference between the two groups was significant (P ＜ 0.01).The optical density ratio of KLF6 mRNA were 0.1586±0.1071 and 0.8899±0.0638 in the gastric cancer and cancer adjacent tissue respectively,the difference between the two groups was significant (P ＜ 0.01).Conclusion KLF6 expression is low in gastric carcinoma,and moreover,KLF6 expression is significantly lower in poorly differentiated cancers than the well differentiated gastric cancers,there are negative correlation between KLF6 and gastric cancer,therefore KLF6 could be a useful marker for gastric cancer.

Progress in surgical treatment of colon cancer / 国际肿瘤学杂志

In recent years,some aspects of the standardized resection of colon cancer,metastases,recurrent tumor therapy and laparoscopic applications have new concepts.In particular,the view of complete mesocolic excision(CME) is more scientific and effective from the level of embryonic development and anatomy,which lays the foundation for controlling the quality of colon surgery.

Mechanism and expression of KLF6 tumor suppressor gene in related tumors / 国际肿瘤学杂志

It has been revealed that the major mechanism of KLF6 is to upregulate p21 in an p53-independent manner leading to inhibition of cell proliferation. Lacking of KLF6 activity or its abnormal expression may be related to multiple tumors'development and prognosis such as prostate cancer, liver cancer, gastric cancer and other tumors. Furthermore, KLF6 may become a novel candidate for molecular target therapy.