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 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.

Objective:To explore the relation among self-esteem, psychological flexibility and mental health in medical students, and to provide scientific reference for mental health education for medical students.Methods:A total of 788 medical students selected from a medical university in Chongqing City were investigated with the symptom checklist 90 (SCL-90), self-esteem scale (SES), acceptance and action questionnaire-Ⅱ (AAQ-Ⅱ), and cognitive fusion questionnaire-fusion (CFQ-F). SPSS 22.0 software was used for statistical analysis. T test, ANOVA, correlation analysis and tests for mediation effects were conducted. Results:There were significant differences in self-esteem and mental health level among medical students in gender and different grades ( t=-2.55, P<0.05; F=6.53, P<0.05). Mental health, self-esteem and psychological flexibility of medical students were correlated in pairs ( r=-0.528-0.694, P<0.01). Psychological flexibility played a partial mediation role between self-esteem and mental health of medical students, and the mediating effect accounted for 60.03% of the total effect. Conclusion:Self-esteem can directly predict the mental health of medical students, and can also indirectly affect mental health through psychological flexibility. Medical universities should carry out psychological education and promotion work with pertinence.

OBJECTIVE: To investigate the psychological and behavior status of minor children of medical staff in Hubei province during the coronavirus disease 2019 (COVID-19) epidemic. METHODS: A cross-sectional questionnaire survey was conducted through WeChat from March 13 to 15, 2020, which included a general data questionnaire and Conners parental assessment questionnaire (PSQ). The questionnaires received from outside of Hubei province were excluded through IP address, and the questionnaires with answer time <150 s were also excluded. The influence of parental work status on the psychological behavior was analyzed in children of different age groups. RESULTS: A total of 391 valid questionnaires were collected, there were 207 males (52.9%) and 184 females (47.1%); 91 (23.3%) aged 3 to 6, 183 (46.8%) aged 6 to 10, and 117 (29.9%) aged 10 to 16. Both parents were medical staff in 87 participants(22.3%), one parent was medical staff in 139(35.5%) participants, and no parents were medical staff in 165 (42.2%) participants. In 3-<6 years group, there was no significant difference in the PSQ scores of the children in each factor level (all >0.05) between children with parents as medical staff and those without. In 6-<10 years group, children with both parents as medical staff had higher hyperactivity-impulse factor score, learning problem factor score and total score than those without parents as medical staff (all <0.05), while they had higher learning problem factor score than those with one parent as medical staff (<0.05); the anxiety score of children with one or both parents as medical staff was higher than that of those without parents as medical staff (all <0.05). In 10 to 16 years group, the behavior problems, learning problems, hyperactivity-impulse, more dynamic index and the total score in children with one parent as medical staff were lower than those with both parents as medical staff or without parents as medical staff (<0.05 or <0.01); while there were no significant differences in psychosomatic problems, anxiety factor scores between children with one parent as medical staff and other two groups (all >0.05). CONCLUSIONS s During COVID-19 epidemic period, the psychological and behavior status of minor children of Hubei medical staff with different ages shows differences with those without parents as medical staff, particularly in 6-<10 years and 10 to 16 year groups. It is necessary to pay attention to the psychological and behavioral status of children of medical staff in these age groups.
Adolescent ; Betacoronavirus ; Child ; Child, Preschool ; China ; epidemiology ; Coronavirus ; Coronavirus Infections ; Cross-Sectional Studies ; Female ; Humans ; Male ; Medical Staff ; statistics & numerical data ; Mental Health ; statistics & numerical data ; Pandemics ; Pneumonia, Viral ; Surveys and Questionnaires

Objective:To evaluate the accuracy of measuring the siae of atrial septal defect(ASD) by transthoracic echocardiography(TTE) on " compression of right superior pulmonary vein sheath during operation" (compression-size) using multi-layer perceptron.Methods:From January 2016 to January 2019, 460 cases of ASD with soft margin, thin growth or central type with atrial septal tumor in the First Hospital Affiliated of Air Force Medical University were analyzed retrospectively. The age was (34.32±18.84)years, 129 males and 331 females. Preoperative TTE and intraoperative TTE were performed to measure the size of ASD and compression-size. With the final occluder size selected as the dependent variable, the preoperative and intraoperative ultrasound measurements were used as covariates, and all patients were randomly divided into training set, test set and verification set according to the proportion of 5∶2∶3, which were imported into multi-layer perceptron. Gradient descent method was used to optimize and adjust the weight, and 10 operations were carried out respectively, and the average value was calculated to evaluate the two ultrasound methods for blocking.Results:The mean values of ASD were (15.26±5.33)mm for preoperative, (23.83±6.39)mm for compression-size intraoperative TTE, and (25.14±6.55)mm for the occluder, respectively. The difference was statistically significant (χ 2=850.450, P<0.001). There were significant differences between the pairwise ( P<0.001). Ten times of multi-layer perceptron were used to obtain a training model for predicting the size of the occluder based on preoperative transthoracic ultrasound and TTE measurement after right upper pulmonary vein sheath compression. The average relative error of the model obtained by preoperative ultrasound measurement in the validation set was (16.55±0.02)%, and that of the model obtained by intraoperative ultrasound measurement in the validation set was (4.81±0.01)%. The difference between the two methods was statistically significant ( t=16.185, P<0.001). Conclusions:It is more accurate to measure the ASD size for selection of occluder by the use of the right superior pulmonary vein sheath compression and TTE, especially for ASD patients with soft margin, thin growth or atrial septal tumor.

Objective To compare the effectiveness and safety of endoscopic submucosal dissection ( ESD) with endoscopic piecemeal mucosal resection ( EPMR) for early esophageal cancer and precancerous lesions with length more than 5 cm. Methods A retrospective analysis was performed on data of 85 patients diagnosed as early esophageal cancer and precancerous lesions with length more than 5 cm in Fujian Medical Association of Early Esophageal Carcinoma from January 2012 to July 2017. The patients were divided into ESD group (52 cases) and EPMR group (33 cases), and the effectiveness and safety between the two groups were compared. Results There was no significant difference on the complete resection rate between the two groups[86. 5％ (45/52) VS 87. 9％ (29/33), P>0. 05]. The operative time (58. 53±30. 50 min VS 32. 06±9. 12 min), postoperative fasting time (4. 18±1. 30 d VS 3. 67±0. 96 d), postoperative hospital-stay time (7. 45±2. 44 d VS 6. 54±1. 73 d), and postoperative antibiotics using time (3. 48±2. 33 d VS 1. 96±2. 20 d) in ESD group were higher than those in EPMR group (all P<0. 05). There were no significant difference in the rate of intraoperative complication and short-term postoperative complication, such as fever, chest pain, and postoperative bleeding, between the two groups ( all P>0. 05 ) . But the postoperative stricture rate of ESD group was higher than that of EPMR group[23. 1％ (12/52) VS 6. 1％(2/33), P<0. 05]. During the follow-up of 3-63 months, 5 cases recurred in ESD group and 1 case in EPMR group, with no significant difference ( P>0. 05). Conclusion ESD and EPMR have equivalent efficacy and safety on the treatment of early esophageal cancer and precancerous lesion. EPMR has a shorter operative time, lower rate of post-operative stricture, and is easier to master.

Objective To investigate the clinical effect of "pre-purse-string" suture on submucous gastric lesions of external growth type in endoscopic patients. Methods Clinical data of 27 patients with gastric lesions of external growth type admitted to the digestive endoscopy center of Renmin Hospital of Wuhan University from August 2016 to October 2016 for endoscopic submucosal dissection ( ESD ) were analyzed. Patients were randomly divided into two groups, the experiment group receiving the "pre-purse-string" suture, the control group receiving purse-string suture after ESD. Mean size of the lesions, procedure time, withdrawal time of gastric decompression, and hospitalization time were compared. Results In the 15 patients of the experiment group, there were 3 cases whose lesions were located in gastric antrum, 6 in gastric body and 6 in gastric fundus. In the 12 cases of the control group, 3 lesions were located in gastric antrum, 5 in gastric body and 4 in gastric fundus. All procedures were successfully completed in endoscopy. No obvious postoperative complications occurred. The mean size of lesions was 2. 5 cm × 3. 2 cm in the experiment group,and 2. 4 cm×3. 0 cm in the control group (P=0. 63). The operation time was 28. 0-43. 0 min (35. 8±6. 1 min) in the experiment group, and 45. 6-68. 8 min (48. 8±5. 3 min) in control group ( P<0. 01) . Conclusion "Pre-purse-string" technique is of clinical effect on gastric submucosal tumor of external growth.

Objective To compare the advantages and disadvantages of the amplification refractory mutation system -polymerase chain reaction (ARMS-PCR) with restriction fragment length polymorphism polymerase chain reaction(RFLP-PCR) technology, then explore its application in detection and analysis of single nucleotide polymorphism (SNP). Methods By using ARMS-PCR and RFLP-PCR the polymorphisms of the MMP-2 in cervical cancer and the normal-control group were analyzed. The research sites were-1306 C/T.The final result was verified by DNA sequencing. Results The results of amplified used ARMS-PCR showed that the genotypes of the SNP site in MMP-2 gene promoter were CC, CT, TT, and the DNA fragments were corresponding with the results of DNA sequencing. Conclusion ARMS-PCR technology has the advantages of lower cost time-saving simple operation and reliable results, while has a high value for research of SNP.

This study was aimed to investigate the changes of hemodynamic parameters, pathology and c kit mRNA expression in myocardium after acute myocardial infarctionin (AMI) in rats, and to elucidate the relationship between these three kinds of changes. Sixty six adult male SD rats were randomly divided into normal group, Sham groups and ligation groups. The rat model of AMI was set up by ligating the left anterior descending artery. Hemodynamic parameters, pathological changes and c kit mRNA expression in myocardiam were examined. The results revealed that there were no statistically significant differences in hemodynamic parameters between normal group and Sham groups. Compared with the normal group, all ligation groups exhibited significantly decreased left ventricular systolic pressure (LVSP) and +/-dp/dtmax (P<0.01), and increased left ventricular end diastolic pressure (LVEDP, P<0.01). In the other ligation groups, compared with 6th hour group after ligation, there appeared striking increase of LVSP, LVEDP and +/-dp/dtmax (P<0.05). HE staining in myocardiam showed that there are necrosis and derangement at 24th hour group after ligation ,and a great number of inflammatory cells infiltration around the infarct zone at 3rd day group after ligation, and granulation tissue infiltrated into the infarct zone at 14th day group after ligation. In all five time points groups after ligation, the levels of c-kit mRNA expression were 0.99 fold, 1.06 fold, 1.46 fold, 1.91 fold and 2.67 fold, respectively, compared with Sham groups. The results suggest that cardiac stem cells in myocardium might contribute to the role of regenerating myocardium via self proliferation after acute myocardial infarction, but further investigation is still needed.
Animals ; Hemodynamics ; physiology ; Male ; Myocardial Infarction ; metabolism ; pathology ; physiopathology ; Myocardium ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; Proto-Oncogene Proteins c-kit ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stem Cells ; cytology

This study was aimed at observing the effects of ovariectomy and estradiol on the microarchitecture of cancellous bone and exploring the influence of microarchitectural change on the biomechanical properties. Thirty 6-month-old unmated female SD rats were randomly divided into 3 groups (10 rat each): sham-operated control group (Sham), ovariectomized group (OVX)and Estradiol Benzoate treated group (EBT). All rats were housed in standard environmental conditions. Five months after operation, the rats were sacrificed. The biomechanical properties of the third lumbar vertebras (L3) were measured with compression testing in vitro. Micro-CT scanning was performed on the fourth lumbar vertebras (L4) in vitro. In comparison with the corresponding variables of Sham, the bone volume fraction (BV/TV) and the trabecular number (Tb. N) of OVX were reduced remarkably, and the trabecular separation (Tb. Sp) and the structural model index (SMI) of OVX were enhanced obviously. These facts implicated that the bone trabecular plate-like structure of OVX were decreased. BV/TV, Tb. N and the trabecular thickness (Tb. Th) of EBT were greater than those of OVX. Tb. Sp and SMI of EBT were much smaller than those of OVX. The results of mechanical test showed that the maximum forioe (Fmax), the maximum stress (sigmamax) and the elastic modeulus (E) of the lumbar vertebral cancellous bone of OVX were declined sharply, while the aforesaid biomechanical index of EBT was improved distinctly. The performance of three-dimensional micro-CT and the mechanical testing to assess microarchitecture of cancellous bone are useful for evaluating the state of osteoporosis and the antiosteoporotic effect of agents.
Animals ; Biomechanical Phenomena ; Estradiol ; pharmacology ; Female ; Imaging, Three-Dimensional ; Lumbar Vertebrae ; diagnostic imaging ; pathology ; Osteoporosis ; pathology ; Ovariectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tomography, X-Ray Computed