Functional mechanisms of WRKY transcription factors in regulating plant response to abiotic stresses / 生物工程学报

WRKYs is a unique family of transcription factors (TFs) in plants, and belongs to the typical multifunctional regulator. It is involved in the regulation of multiple signaling pathways. This type of transcription factor is characterized to contain about 60 highly conservative amino acids as the WRKY domain, and usually also has the Cys2His2 or Cys2His-Cys zinc finger structure. WRKYs can directly bind to the W-box sequence ((T)(T) TGAC (C/T)) in the promoter region of the downstream target gene, and activate or inhibit the transcription of the target genes by interacting with the target protein. They may up-regulate the expression of stress-related genes through integrating signal pathways mediated by abscisic acid (ABA) and reactive oxygen species (ROS), thus playing a vital role in regulating plant response to abiotic stresses. This review summarizes the advances in research on the structure and classification, regulatory approach of WRKYs, and the molecular mechanisms of WRKYs involved in response to drought and salt stresses, and prospects future research directions, with the aim to provide a theoretical support for the genetic improvement of crop in response to abiotic stresses.

Clinical characteristics and prognosis analysis of B-cell chronic lymphoproliferative disorders unclassified / 白血病·淋巴瘤

Objective:To explore the clinical features and prognostic related factors of B-cell chronic lymphoproliferative disorders unclassified (B-CLPD-U).Methods:The clinical data of 39 patients diagnosed with B-CLPD-U in the First Affiliated Hospital of Harbin Medical University from January 2012 to January 2019 were retrospectively analyzed. Patients were regularly treated with COP regimen (30 cases) or fludarabine regimen (9 cases). The χ 2 test was used to analyze the relationship between the clinical characteristics and the efficacy of the patients. The Kaplan-Meier method was used for survival analysis and the log-rank test was used for single factor analysis. The Cox proportional hazard regression model was used for multivariate analysis, and the receiver operating characteristic (ROC) curve was used to analyze the value of platelet-to-lymphocyte ratio (PLR) in prognostic evaluation. Results:Among 39 patients, there were 24 males and 15 females, and the median age was 60 years old (37-78 years old). The international prognostic index (IPI) score was 0 to 2 in 19 cases (48.7%), and 3 to 5 in 20 cases (51.3%). The overall response rate (complete remission plus partial remission) rate (ORR) of the patients was 82.1% (32/39). The ORR of patients with normal lactate dehydrogenase (LDH) (≤ 245 U/L) was higher than that of patients with elevated LDH (> 245 U/L). The ORR of patients with Ann Arbor stage Ⅰ-Ⅱ was higher than that of patients with stage Ⅲ-Ⅳ, and the differences were statistically significant [95.5% (21/22) vs. 64.7% (11/17), 100.0% (15/15) vs. 70.8% (17/24), all P < 0.05]. At the end of the follow-up in October 2019, 31 cases (79.5%) survived and 8 cases (20.5%) died of 39 patients; the median overall survival(OS) time was 40.0 months (95% CI 36.0-55.2 months). Univariate analysis showed that patients with elevated LDH and age over 60 years had poor OS, and the difference was statistically significant (all P <0.05), while there were no statistically significant differences in OS between patients with gender, Ann Arbor staging, IPI score, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) score, anemia, B symptoms, COP-based chemotherapy or fludarabine-based chemotherapy, and different absolute lymphocyte (ALC) stratification (all P > 0.05). Multivariate analysis showed that LDH level ( HR = 0.411, 95% CI 0.172-0.981, P = 0.045) and age ( HR = 2.242, 95% CI 1.045-4.808, P = 0.038) were independent influencing factors of OS (both P < 0.05). The median PLR was 59.07 (1.18-276.26). ROC curve analysis showed that the area under the curve for PLR to predict OS was 0.565. Conclusion:B-CLPD-U is more common in middle-aged and elderly patients, and it is more commonly found in men than women. Elevated LDH and age over 60 years are independent risk factors for survival of patients with B-CLPD-U. The evaluation of sensitivity and specificity of the prognosis in B-CLPD-U patients by using PLR will be not that ideal.

Diagnosis and treatment progress of Hodgkin lymphoma / 肿瘤研究与临床

Hodgkin lymphoma (HL) is a kind of malignant tumors originating from lymphoid hemopoietic tissues and often involves lymphatic system.HL is a kind of highly curable lymphomas,and the assessment of prognostic factors is important for the diagnosis and treatment of this disease.In recent years,the international research focuses on the reasonable and individualized comprehensive treatment mode of radiotherapy and chemotherapy,the exploration of new drugs and new chemotherapy protocols,in order to further improve the survival rate of patients.Staging criteria from several research organizations have played the guiding role in the therapeutic strategy of risk adjustment.Some researches have proposed low toxic and effective combined chemotherapy regimens,radiotherapy and new targeted drugs guided by positron-emission tomography.Combined with the National Comprehensive Cancer Network (NCCN) in 2017 guidelines,this paper reviews the progresses of clinicopathological manifestations,differential diagnosis and treatment regimens of HL.

The Treatment and Progress in Consolidation Therapy of APL / 现代生物医学进展

Acute promyelocytic leukemia (APL) was considered to be the most rapidly fatal leukemia,because of serve clinical manifestation,high rate of early death and the low cure rate.APL has achieved great success due to the application of ATRA and ATO.Although the complete remission rate is about 90％,the relapse rate has been reported to be as high as 15％-30％.So reducing the recurrence and improving long-time survival have become the focus of the study.Choosing the reasonable treatment after remission is very important.The post remission therapy usually include consolidation therapy and maintenance therapy,but the optimal strategy has been controversy.Therefore,this artical will review the literature of APL in consolidation therapy.

Efficacy and safety of anagrelide in treatment of essential thrombocythemia: multicenter, randomized controlled clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).</p><p><b>METHODS</b>Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.</p><p><b>RESULTS</b>A total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).</p><p><b>CONCLUSION</b>Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.</p>

Expression and significance of β-catenin gene in the tissue of primary central nervous system lymphoma / 白血病·淋巴瘤

Objective To detect the expression of β-catenin in the tissues of primary central nervous system lymphoma (PCNSL), and to discuss its function in PCNSL.Methods The paraffin embedded tissues from 10 patients diagnosed as PCNSL from October 2010 to April 2012 were collected as the experimental group.The paraffin embedded tissues from 10 patients with lymphadenitis were collected as the control group.Quantitative real-time PCR and immunohistochemical method were used to detect the expression of β-catenin in these tissues, and the relationships between β-catenin and clinical data were analyzed.Results Immunohistochemistry results showed that β-catenin protein was localized in the cytoplasm and (or) nucleus.Among 10 PCNSL patients, β-catenin protein was positive in 4 patients, while it was no positive in all of 10 lymphadenitis patients, with the significant differences between both groups (P ＜ 0.05).The β-catenin gene relative expression level was 4.70±0.57 and 1.00±0.27 in the experimental group and the control group, respectively.β-catenin expression was no correlation to age, PS score, cerebrospinal fluid protein level and serum lactate dehydrogenase level of patients with PCNSL.Conclusions Whether in mRNA level or in protein level, β-catenin expression is always high in PCNSL tissues, and its protein is expressed in the cytoplasm, however, this phenomenon was not observed in the tissue of lymphadenitis.

Analysis of residual lymph node from diffuse large B-cell lymphoma after chemotherapy / 白血病·淋巴瘤

Objective To evaluate hemodynamic status,pathological,imaging and ultrasound changes of residual lymph nodes from diffuse large B-cell lymphoma (DLBCL) after chemotherapy and their relationship with clinical treatment after chemotherapy.Methods 50 DLBCL patients undergoing full course of chemotherapy but still bearing residual lymph nodes were examined with ultrasound-guided lymph node biopsy.Some examinations were combined with PET-CT to analyze properties of residual lymph nodes.Results 64 lymph nodes were identified by color Doppler ultrasounda in the 50 DLBCL patients treated with full course of chemotherapy.Among them,53 lymph nodes from 42 patients did not show artery blood flow and HE staining of these lymph node biopsy met the clinical standard for complete remission.For the other 11 lymph nodes from 8 patients,ultrasound examination displayed smrounding blood flow inside.At the same time,PET-CT showed that these lymph nodes had higher SUV values,implying high metabolic state in these tissues,which was in agreement with ultrasonic examination results.However,HE staining of these lymph nodes biopsy demonstrated only residual lesion but no tumor tissue.Conclusions Lymph nodes still exist in DLBCL patients treated with full course of chemotherapy.Ultrasound and PET-CT examination have high accuracy in diagnosing benign and malignant residual lymph nodes in follow-up examination on 4 weeks after chemotherapy showed that lymph nodes are over ＞ 1.5 cm in length and have central or peripheral blood flow.Therefore,PET-CT examination of tumor could be considered as a reference index in characterizing residual tumors after chemotherapy.

Effect of experimental benzolism on marrow erythrocyte micronucleus / 中国综合临床

Objective To investigate the effect of experimental benzolism on marrow eryghrocyte micromucleus.Methods Fifty male KunMingmice(KM)were randomly divided into 5 groups:one control group and four experimental groups with 10 mice in each group.The mice were injected subcutaneously with sodium chloride in control group and benzene in experimental groups on every Monday,Wednesday and Friday for four weeks.Four experimental groups were injected with a dosage of 0.5 ml/kg(group B1),1.0 nd/kg(group B2),1.5 ml/kg(group B3) and 2.0 ml/ks(group B4),respectively.Before and after injection of sodium chloride or benzene weekly.weight was measured,and the alteration of erythrocyte micronucleus in peripheral blood and marrow were detected.Results ① Compared to the control group,several indices were partly changed in B1 and B2 groups,while all indices changed significantly in group B3 and B4 groups four weeks after injection(P<0.01).②The erythrocyte micronucleus rate of experimental mice in peripheral blood and marrow showed ascending tendency with the extension of benzene injection phase,peak emerged in the third week and decreased in the fourth week.③In the 4th week,compared to the control group,the alteration of erythrocyte micronucleus in marrow in all experimental groups were significantly increaged(P<0.05).Conclusions Benzolism may induce the increasing of micronucleus rate of mature erythrocyte in peripheral blood and erythrocyte in marrow.which can be used to detect status of being restrained in marrow erythrocyte series.

Detecting the AChE content of RBC and plasma in the people with paroxysmal nocturnal hemoglobinuria / 中国实用内科杂志

Objective Detect the AChE content of RBC and plasma in the people with PNH.Invstigate the effect of the enzyme in GPI on PNH.Methods Detect the activity of AChE in RBC and plasma in 30 patients with PNH.Results (1)The activity of AChE of RBC in PNH patients was higher than controls,the difference between them having statistic significance,P