Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of ursane triterpenoids 3β,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells.@*METHODS@#CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells.@*RESULTS@#RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK.@*CONCLUSION@#RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.

Influence factors for decreased quality of life in thyroid-associated ophthalmo-pathy patients / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the quality of life in patients with thyroid associated ophthalmopathy in China, to analyze the factors related to the decline of quality of life and to provide evidence for the clinical diagnosis and treatment. <p>METHODS: Totally 125 patients diagnosed with thyroid associated ophthalmopathy from January 2015 to January 2016 at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were included. Clinical data including gender, age, eyelid, conjunctival hyperemia and edema, lacrimal caruncle swelling, degree of proptosis, eyelid retraction volume, vision, diplopia were recorded. TAO-QOL questionnaire were investigated. The content was divided into two dimensions: visual function and appearance. Each dimension contains eight related questions. Final indicators for each dimension was the score. Independent <i>t</i> test, ANOVA and multiple regression analysis were performed using SPSS tactics 22.0 software. <p>RESULTS: Eighty-eight valid questionnaires were included. The average score of visual function was 72.6±28.3 and that of appearance was 66.8±26.0; 28 cases(28/88)were in active phase while 60 cases(60/88)were in inactive phase. Visual function and appearance scores were 59.4±28.8 and 56.1±26.0 in active group; 78.8±26.1 and 71.8±24.6 in inactive group. Active group has decreased score for both visual function sore and appearance score(<i>P</i>=0.002 and <i>P</i>=0.008). The score of patients with mild TAO(26/88 )was 86.2±17.1 and 82.1±17.8; 70.3±28.3 and 63.3±25.5 for moderate-severe patients(55/88), 41.1±34.6 and 37.6±22.7 for extremely severe patients(7/88). The score of both visual function and appearance in severe group were significantly lower than those in the moderate-severe group(<i>P</i>=0.006 and <i>P</i>=0.007).Compared to mild group, those of moderate-severe group were significantly lower(<i>P</i>=0.012, <i>P</i>=0.001).The visual function score of patients in constant diplopia group were significantly lower than the no diplopia group, horizontal or vertical gaze diplopia and inconstant diplopia group(<i>P</i><0.001, <0.001, =0.002). By multivariate regression analysis, we found the factors that influence visual function score were visual acuity and diplopia(<i>R</i>²=0.470), and those correlated to appearance score were exophthalmos, retraction and diplopia(<i>R</i>²=0.375).<p>CONCLUSION: TAO-QoL can be used as a simple and effective tool to evaluate the quality of life in TAO patients. The QoL score is related to disease staging and grading. Thus, shortening the course of active phase, decreasing the degree of diplopia and improving visual acuity are critical ways to improve the quality of life in TAO patients.

Research Progress on Application of CRISPR/Cas Genome Editing Technology in Hematological Diseases -Review / 中国实验血液学杂志

CRISPR/Cas genome editing technology is a newly developed powerful tool for genetic manipulation, which can be used to manipulate the genome at specific locations precisely, to restore the function of genetic defect cells, and to develop various disease models. In recentl years, with the advances of precise genome manipulation, CRISPR/Cas technology has been applied to many aspects of diseases research and becomes an unique tool to investigate gene function and discover new therapeutic targets for genetic diseases. Nowadays, CRISPR/Cas technology has been a hot research point in agriculture, graziery, biotechnology and medicine. This review focuses on the recent advances in CRISPR/Cas technology and its application in hematological diseases.

Research Progress on Long Non-Coding RNA in Hematological Malignancies--Review / 中国实验血液学杂志

Long non-coding RNA (LncRNA) is defined as a class of transcripts more than 200 nucleotides in length and without the protein-coding function. It has been found for years, however, that little is known about the potential role of LncRNA in humans. But recent studies showed that LncRNA can regulate the coding-gene expression and participate in effects of human body. Accumulating evidence demonstrated that LncRNA are involved in cancer incidence, development and progression.With further exploration on the mechanisms of tumors, the relationship between the long non-coding RNA and hematological malignancies increasingly become a hot research. This review focuses on the mechanisms of LncRNA in hematological malignancies.

Expression and Significance of NLRP3, ASC and AIM2 in Patients with Acute Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and significance of NLR family, pyrin domain containing 3 (NLRP3), apoptosis associated speck like protein containing a CRAD (ASC) and absent in melanoma 2 (AIM2) of patients with acute leukemia.</p><p><b>METHODS</b>The petipheral blood samples of 19 patients with ALL and 41 patients with ANLL as the AL group (each 20 cases of newly diagnosed, relapsed and complete remission group) and 20 cases of non-hematologic malignancies as the control group were collected from July 2013 to July 2014 in the First Affiliated Hospital of Gannan Medical University. The expression levels of NLRP3, ASC and AIM2 in peripheral blood plasma were determined by ELISA.</p><p><b>RESULTS</b>The expression levels of NLRP3, ASC and AIM2 in plasma of control and AL complete remission groups were significantly higher than those in newly diagnosed and relapsed groups, and were with statistical significance (P < 0.05), but there were no statistical signifirance between ALL and ANLL groups (P > 0.05).</p><p><b>CONCLUSION</b>The expression of NLRP3, ASC and AIM2 is down-regulated in the patients with acute leukemia, which maybe play a role of anti-leukemia, and provide a laboratory evidence for diagnosis and treatment of patients with acute leukemia.</p>

Expression of HMGB1 and NF-κB in Patients with Acute Leukemia and Its Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression of high mobility group box protein 1 (HMGB1) and nuclear factor-kappa B (NF-κB) in patients with acute leukemia and its significance.</p><p><b>METHOD</b>20 samples of bone marrow and peripheral blood from each acute leukemia groups (newly diagnozed, relapsed and complete remission groups) and 20 samples as control from patients with no-hematologic malignancies were collected. The expression level of HMGB1 in peripheral blood plasma was determined by ELISA; HMGB1 and NF-κB level in mononuclear cells were examined by RT-PCR. Western blot was used to determine HMGB1 and NF-κB protein levels. HMGB1 and NF-κB in bone marrow smears were determined by immnohistochemistry method (IHC).</p><p><b>RESULTS</b>The expression level of HMGB1 obviously increased in patients of newly diagnosed and relapsed groups, as compared with control group there was statistical significance (P < 0.05), but there was no obvious difference in expression level of HMGB1 between complete remission group and control group (P > 0.05). The expression level of HMGB1 and NF-kB in monnuclear cells of bone marrow in newly-diagnosed group and relapsed group was significantly higher than that in control group (P < 0.05), but the expression levels of HMGB1 and NF-kB in complete remisson group did not change (P > 0.05). The results of immnohistochemistry method indicated that the possitive expression of HMGB1 and NF-kB maily was found in bone marrow smears of newly diagnosed and relapsed groups.</p><p><b>CONCLUSION</b>HMGB1 is overexpressed in acute leukemia, which may be involved in the occurrence and development of acute leukemia by activating the NF-κB signaling pathway, HMGB1 may be a important index for observing therapeutic effectiveness and predicting recurrence of acute leukemia.</p>