Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To observe the value of pseudo-continuous arterial spin labeling(PCASL)MRI for evaluating renal function in patients with renal occupying lesions.Methods Totally 56 patients with single renal occupying lesion were retrospectively enrolled.The left and right side kidneys were divided into normal renal function group(normal group,30 ml/min)and damaged renal function group(damaged group,＜30 ml/min)according to glomerular filtration rate(GFR)measured with 99Tcm-DTPA dynamic renal imaging,respectively.The total renal blood flow(tRBF)and cortical renal blood flow(cRBF)were calculated using total nephrometry and cortical nephrometry based on PCASL MRI,respectively,then GFR,tRBF and cRBF were compared between groups on the same side.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of tRBF and cRBF for assessing unilateral renal injury.Pearson correlation analysis was performed to observe the correlations of tRBF and cRBF with GFR.Results GFR,tRBF and cRBF in left/right damaged group were all significantly lower than those in ipsilateral normal group(all P＜0.05).AUC of tRBF and cRBF for assessing left renal injury was 0.823 and 0.813,respectively,being not significantly different(P＞0.05).AUC of tRBF and cRBF for assessing right renal injury was 0.940 and 0.922,respectively,being not significantly different(P＞0.05).No obvious correlation of bilateral tRBF nor cRBF with GFR was found(all P＞0.05).Conclusion PCASL MRI could effectively evaluate renal function in patients with renal occupying lesion,and the efficacy of total nephrometry was comparable to that of cortical nephrometry.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted Recommendations on Management of Gynecological Malignancies during the COVID-19 Pandemic based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.

BACKGROUND:There are various therapies for children limb fractures involving the epiphysis or the metaphysis. According to the different methods, studies on the growth of the epiphyseal plate are a lot, most of which focus on the effects of Kirschner wires with different diameters or holow screw internal fixation on the development of epiphyseal plate. However, there are rare studies on the influence of cross-epiphyseal plate internal fixation on the growth of epiphyseal plate as wel as the influence level. OBJECTIVE:To prepare a peri-epiphyseal fracture model in young rabbits and to observe the effects of cross-epiphyseal plate implantation and removal on the growth of epiphyseal plate. METHODS: Traverse fracture models were made 5 mm above the right femoral distal epiphyseal plate of 60 young rabbits, and then fixed with suitable “L” steel plate and four screws across the epiphyseal plate and peri-epiphyseal fracture line. The left side served as control. Eight rabbits were kiled and observed at 2, 4, 8, 12 weeks after modeling, respectively, to take out the femoral specimens for measurement of femoral length, thickness of the epiphyseal plate, and number of mastocytes per unit column. Histopathology observation was done and changes in mastocytes and thickness of the epiphyseal plate were detected. Another seven rabbits were selected to remove the metal plate, continued to feed for 2 weeks and finaly executed to observe the above-mentioned indexes. RESULTS AND CONCLUSION: (1) There were significant differences in the above indexes between the plate and control groups at 4, 8, 12 weeks after modeling (P < 0.05 orP< 0.001) but not at 2 weeks after modeling (P> 0.05). These findings indicate that within 2 weeks after cross-epiphyseal plate internal fixation, proper pressue has no remarkable influence on the growth of epiphyseal plate; but after persistent internal fixation (> 4 weeks), the growth of epiphyseal plate can be partialy or completed retarded. (2) At 2 and 4 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length, thickness of the epiphyseal plate and mastocyte counting per unit column were improved to different extents, and there were no differences between the plate and control group (P > 0.05). At 8 and 12 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length and thickness of the epiphyseal plate were shortened, and the number of mastocytes per unit column was decreased obviously, which significantly differed from the control group (P < 0.001). These findings indicate that the chondrocytes in the proliferative and hypertrophy layers lose the differentiation and proliferation abilities, and the femoral length and epiphyseal plate thickness are difficult to recover.