Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Clinic analysis of 198 elder patients with maxillofacial fracture / 华西口腔医学杂志

OBJECTIVE@#The purpose of the study was to analyze the characteristics of elder patients with maxillofacial fracture.@*METHODS@#We retrospectively analyzed the characteristics of maxillofacial fractures in the elder patients, who were treated from July 2010 to October 2017. The clinical characteristics of the etiology, fracture site, combined injury, systemic disease, and treatment method were analyzed.@*RESULTS@#In the 198 elderly patients with maxillofacial fractures, the male-to-female ratio was 3.95︰1, and the mean age was 66.15 years old. Traffic accident injury (78 patients, 39.39%), fall injury (49 patients, 24.75%), high fall injury (33 patients, 16.67%) were the main factors of maxillofacial fracture in elderly patients. The most frequently observed fracture site was the mandible (120 patients). A total of 60 patients demonstrated associated injuries, in which limb injuries were the most prevalent (28 patients); whereas 66 patients had other systemic medical conditions, in which cardiovascular diseases was the most frequent (50 patients). The main treatment method of 198 patients was rigid internal fixation with small or micro-plates.@*CONCLUSIONS@#Falling and traffic accidents are the main factors of maxillofacial fracture in elderly patients. Thus, interference measures should be observed for the prevention of maxillofacial fractures in elderly patients.

Anti-Leukemia Effect and Mechanism of Oridonin on Imatinib-Sensitive and Imatinib-Resistant K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the molecular mechanism of resistance to imatinib in K562 cells(K562-R) and the anti-proliferative effect of oridonin (OR), as well as its mechanism in imatinib-sensitive and imatinib-resistant K562 cells (K562-S and K562-R cells).</p><p><b>METHODS</b>The expression of p-Lyn in K562-S and K562-R cells were detected by Western blot. The anti-proliferative effect of OR in K562-S and K562-R cells was assayed by MTT, the morphological changes were examined with microscope, the cell apoptosis was detected by flow cytometry, the expressions of BCL-2 and Akt/mTOR signaling pathway were detected by Western blot.</p><p><b>RESULTS</b>The over-expression of p-Lyn was detcected in K562-R cells, OR inhibited the proliferation of K562-S and K562-R cells and the value of ICwas 4.23±1.30, 4.97±2.23 µmol/L, respectively. The apoptotic rate was obviously enhanced after OR treatment for 24 h, compared with control group. OR down-regulated the expression of p-Lyn, mTOR signaling pathway and BCL-2 protein.</p><p><b>CONCLUSION</b>Over-expression of p-Lyn may be involved in the mechanism of resistance to imatinib. OR can inhibit the proliferation of K562-S and K562-R cells through down-regulating p-Lyn, inhibiting mTOR signaling pathway and down-regulating expression of BCL-2 protein.</p>

Anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia cell SUP-B15 / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15.</p><p><b>METHODS</b>Human Ph(+) ALL cell line was cultured in vitro. The 50% inhibition concentration (IC(50)) of oridonin against SUP-B15 cell line was examined using modified MTT assay. The cellular morphologic changes were observed using a light microscope. The percent of apoptosis of SUP-B15 cell line after drug treatment was evaluated by flow cytometric analysis. The active levels of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK, STAT5 signaling pathways and the expression levels of Bcl-2 and BAX were examined by Western blot.</p><p><b>RESULTS</b>Oridonin inhibited the growth of SUP-B15 cell line in both time- and dose-dependent manner with the IC(50) of oridonin as (7.08 ± 1.21) µmol/L after 72 h treatment. The cellular membrane of SUP-B15 cell line treated with oridonin became unsharp, some of them disintegrated. Oridonin induced apoptosis in SUP-B15 cell line with the apoptosis rates following 0, 5, 10 µmol/L oridonin treatment for 24 h were (6.67 ± 0.83)%, (18.30 ± 1.79)% and (37.63 ± 7.12)%, respectively. Oridonin inhibited activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, which were constitutively activated in SUP-B15 cell line, down-regulated the level of anti- apoptotic protein Bcl-2 and up-regulated the expression of pro-apoptotic protein Bax.</p><p><b>CONCLUSION</b>Oridonin exerted anti-leukemia effect in Ph(+)ALL cell line SUP-B15 by inhibiting the activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, down-regulating the expression of Bcl-2 and up-regulating the expression of BAX.</p>

The effect of knockdown of transcription factor SCL/TAL-1 gene on the erythroid differentiation in EPO-induced K562 cell line / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the role of transcript factor SCL/TAL-1 gene in the erythroid differentiation through the knockdown of SCL/TAL-1 mRNA by RNA interference.</p><p><b>METHODS</b>The plasmid of pTRIP-dU3-RNAiTALh-EF1a-GFP with SCL/TAL1 shRNA was transfected into EPO-induced K562 cell line with erythroid differentiation via lentiviral vector system and the expression of SCL/TAL-1 mRNA decreased. The plasmid pTRIP-dU3- RNAiluc-EF1-GFP expressing EGFP gene was as control. The mRNA levels of SCL/TAL-1 and erythroid related RhD, GPA, CD47 in the cell lines were detected by RT-PCR, and erythroid antigen CD71, CD235a were examined by flow cytometry.</p><p><b>RESULTS</b>(1) After 48 h of transfect, more than 95% of K562 cells were GFP positive, indicating the infection rate of the plasmids in the K562 cells more than 95%. (2) The results of RT-PCR showed SCL/TAL-1 mRNA expression in the K562 cell line of knockdown of SCL/TAL-1 was significantly lower than that in the control (P < 0.05). The mRNA levels of CD47 and RhD were also significantly lower, however, GPA decreased slightly in comparison with the control. (3) The expressions of CD71 and CD235a markedly reduced in the K562 cell line of knockdown of SCL/TAL-1 with positive rates as 10.4% and 76.5%, while the positive rates in the control as 94.3% and 83.6%.</p><p><b>CONCLUSION</b>Our findings suggested that transcription factor SCL/TAL-1 might play an positive role in erythroid differentiation.</p>

Cross reactivity of mimotopes of hepatitis C virus hypervariable region 1 / 病毒学报

The cross reactivity of mimotopes of hepatitis C virus (HCV) hypervariable region 1 (HVR1) was investigated to obtain epitopes that have high cross reactivity. Five expression vectors encoding B cell mimotopes fused with Trx were constructed, and the mimotope proteins were purified. The cross reactivity of mimotope proteins with HCV positive sera was determined by ELISA. HCV pseudotype particles (HCVpp) were generated and applied to evaluate neutralization effects of the sera of BALB/c mice immuned with the mimotope proteins on infection of Huh7. 5 cells. Our data showed that the mimotope proteins (P1, P2, P5, P6, P8) could react to the HCV positive sera. The HCVpp infection inhibition of the sera of BALB/c mice immuned with P6 or P8 was detectable. These results suggest that the mimotopes may be valuable in the studies of anti-HCV infection and development of HCV vaccines.