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.

Left ventricular pseudoaneurysm(LVPA) is a rare type of abnormal ventricular wall bulge formed by injury to the inner wall of the left ventricle. The exterior wall only consists of epicardium or/and pericardium. In a systematic literature review, myocardial infarction(55%), surgery(33%), and trauma(7%) are the top three associations. Being affected by the high pressure of the left ventricle, LVPA has the risk of enlargement and rupture, which can lead to sudden death. The treatment of LVPA consists of three main modalities: medication, surgery, and transcatheter closure. In the past, surgery was the preferred treatment for LVPA, but the surgery was highly invasive, traumatic, and associated with increased risks. In recent years, transcatheter closure has been developed and applied clinically with good results. The benefits of minimal invasiveness and quick recovery have emerged as a popular treatment for LVPA. Currently, the etiology, formation, and treatment of LVPA are not clearly defined. Large-sample studies and authoritative guidelines to guide the treatment are scarce. The timing, imaging modality, and access routes to LVPA for both surgery and transcatheter closure are still controversial. In this article, we review the relevant literatures and draw the following conclusions as: (1) Diagnostic workup is essential for anatomical characterization of LVPA, which is mandatory to guide the decision on surgical methods.(2) For a subset of patients with LVPA and a well-defined fibrotic neck, and deemed at high surgical risk, transcatheter closure of the cavity has been described with encouraging results.

Left ventricular pseudoaneurysm(LVPA) is a rare type of abnormal ventricular wall bulge formed by injury to the inner wall of the left ventricle. The exterior wall only consists of epicardium or/and pericardium. In a systematic literature review, myocardial infarction(55%), surgery(33%), and trauma(7%) are the top three associations. Being affected by the high pressure of the left ventricle, LVPA has the risk of enlargement and rupture, which can lead to sudden death. The treatment of LVPA consists of three main modalities: medication, surgery, and transcatheter closure. In the past, surgery was the preferred treatment for LVPA, but the surgery was highly invasive, traumatic, and associated with increased risks. In recent years, transcatheter closure has been developed and applied clinically with good results. The benefits of minimal invasiveness and quick recovery have emerged as a popular treatment for LVPA. Currently, the etiology, formation, and treatment of LVPA are not clearly defined. Large-sample studies and authoritative guidelines to guide the treatment are scarce. The timing, imaging modality, and access routes to LVPA for both surgery and transcatheter closure are still controversial. In this article, we review the relevant literatures and draw the following conclusions as: (1) Diagnostic workup is essential for anatomical characterization of LVPA, which is mandatory to guide the decision on surgical methods.(2) For a subset of patients with LVPA and a well-defined fibrotic neck, and deemed at high surgical risk, transcatheter closure of the cavity has been described with encouraging results.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Objective:To identify risk factors associated with mandibular osteoradionecrosis (ORN) in oral and maxillofacial cancer patients following radiotherapty and to provide scientific basis for the etiological research and clinical prevention of mandibular ORN.Methods:A retrospective study was conducted in patients with oral and maxillofacial-head and neck cancer during the period from January 2013 to December 2015. Influential factors related to mandibular ORN were screened by single factor analysis, Lasso and Logistic regression analysis.Results:A total of 757 patients were analyzed, and the total incidence of mandibular ORN was 12.0%(91/757). There were 443 males and 314 females, aged (51.8±13.7) years. Thirty-five related factors were screened to 28 by single factor analysis. It was determined by Lasso regression analysis that, radiation doses ( OR=1.135, P=0.034, 95% CI: 1.089-1.232), T classification ( OR=2.586, P=0.001, 95% CI: 1.482-4.512), mandibular surgery ( OR=9.101, P<0.001, 95% CI: 2.796-29.630), periodontitis ( OR=6.089, P<0.001, 95% CI: 2.708-13.693), diabetes ( OR=4.467, P=0.002, 95% CI: 1.705-11.704), tooth extraction after radiotherapy ( OR=3.228, P=0.001, 95% CI: 1.640-6.350), dental caries ( OR=2.911, P=0.009, 95% CI: 1.300-6.516), periapical periodontitis ( OR=2.726, P=0.016, 95% CI: 1.209-6.145), smoking ( OR=4.438, P=0.002, 95% CI: 1.702-11.571) and unilateral/bilateral radiotherapy ( OR=2.225, P=0.028, 95% CI: 1.090-4.545) were significantly associated with developing mandibular ORN. Conclusions:Ten main risk factors for mandibular ORN were identified through the single center, large sample, retrospective analysis, which has a certain value for clinical prevention of mandibular ORN. Prospective, randomized controlled trials and long-term follow-up are still needed.

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K(KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.

Purpose To investigate the reproducibility and risk factors of aortic distensibility quantification in patients with abdominal aortic aneurysm using multi-slice spiral CT.Materials and Methods The abdominal aortic computed tomography angiography data of 54 patients with infrarenal abdominal aortic aneurysm were prospectively studied.64-muti detector spiral CT,retrospective ECG-gating and segment data collecting scanning were all carried out.The aortic distensibility,D value,and pulse wave velocity at renal artery level and infrarenal artery level were calculated using semiautomatic segmentation software.The difference of aortic distensibility at different levels was compared,and consistency test was performed.Results The D value at renal artery level and infrarenal artery level of abdominal aortic aneurysm was (1.05 ±0.22)×10-5/Pa and (0.49± 0.18)× 10-5/Pa,respectively;and the corresponding pulse wave velocity was (9.68± 1.09) m/s and (14.96 ±4.01) m/s,respectively.The intraclass correlation coefficient of intra-and interobserver at renal level was 0.92 and 0.79,while it was 0.85 and 0.79 at inffa level.The Bland-Altman graph showed that the vast majority of points were within the 95％ CI,the difference of intraobserver between the two positions was 0.017×105/pa and 0.010×10-5/Pa,and the difference of interobserver was 0.013×105/Pa and 0.018×10-5/Pa.Multivariate analysis of all these variables showed aortic distensibility to be independently correlated to body mass index,pulse pressure,diastolic pressure and abdominal aortic aneurysm diameter (R2=0.68).Conclusion The quantification of aortic distensibility using multi-slice spiral in patients with abdominal aortic aneurysm shows high stability.Taking into consideration of the relationship between different risk factors and the incidence of abdominal aortic aneurysm can lead to a better clinical approach.

Objective To investigate the clinical value of high resolution ultrasound combined with radiological imaging in the diagnosis of Meckel′s diverticulitis (MD),and to analyze the causes of missed diagnosis as well as misdiagnosis by ultrasound.Methods The image data of 61 patients with MD were retrospectively analyzed,the essentials and the causes of missed diagnosis as well as misdiagnosis of ultrasound were summarized and compared with the results of operation,CT,gastrointestinal contrast,as well as radionuclide.Results The patients were divided into simple type(18,29.5%) and complex type(43,70.5%) according to ultrasonography.The simple type diagnostic accuracy rate was 100%,the ultrasonography showed the right lower abdominal tubular bowel shadow or cystic echo mass,and the structure of diverticulum could clearly showed by ultrasound.In another side,the complex type diagnostic accuracy rate was 55.8%,the ultrasonography showed the right lower abdominal mixed echo mass or concomitant with other alimentary tract malformation,while the diverticulum structure was difficult to be distinguished.The diagnostic accuracy rate of radionuclide imaging was 83.6%,CT was 37.0%,while gastrointestinal contrast was 30.0%.Among 19 cases of misdiagnosis by ultrasound,13 cases of MD were confirmed by radionuclide and CT examination,the diagnostic accuracy rate of ultrasound combined with radiological imaging diagnosis was 90.2%.Conclusions The sonographic features of MD are lack of specificity,especially in the complex type,while the patients with recurrent hemafecia or acute abdomen should be alert to the presence of MD.Patients who are suspected of MD by ultrasound diagnosis should also be examined by radiological imaging in order to make an early diagnosis and surgical treatment to improve the prognosis of patients.

Objective To investigate the clinical value of ultrasonic diagnosis for neonatal annular pancreas,analyze the reasons of missed diagnosis and misdiagnosis,and improve diagnostic accuracy of ultrasonography for this disease.Methods Clinical data of 98 newborns with annular pancreas confirmed by gastrointestinal contrast and surgery were analyzed retrospectively.Preoperative ultrasonogram were compared with the result of gastrointestinal contrast and surgery.Ultrasound images failed to be correctly dignosed were further studied to summarize diagnostic points for this disease.Results Among the 98 cases, 75 were correctly diagnosed by ultrasound with a diagnostic accordance rate of 76.5%,1 8 were missed diagnosed and 5 were misdiagnosed with a total misdiagnosis rate of 23.5%.Ten cases associated with other congenital gastrointestinal tract anomalies were missed diagnosed due to ignoring scanning pancreas.Five cases were missed diagnosed due to obvious intestinal cavity flatulence.Three cases were missed diagnosed due to lack of awareness of the disease.Five cases were misdiagnosed for duodenal stenosis or duodenal atresia.Conclusions Ultrasound has important diagnostic value for neonatal annular pancreas,providing the dignostic evidences for clinical treatment.Thus it can be used as the preferred auxiliary examination of the disease.Since annular pancreas is often accompanied by other gastrointestinal malformations and can be interfered by abdominal gas,missed diagnosis and misdiagnosis occurred easily.To improve the accuracy of ultrasonic diagnosis,all causes of neonatal gastrointestinal tract obstructions should be considered during the examination.

OBJECTIVETo explore whether docetaxel-resistant cells (MCF-7/Doc) and doxorubicin-resistant cells (MCF-7/ADM) can secrete Exosomes and their potential role in cell-cell drug-resistance transfer.

METHODSExosomes were extracted from the cell culture supernatants of MCF-7/Doc and MCF-7/ADM cells by fractionation ultracentrifugation, and were identified by transmission electron microscopy and Western blot analysis. GFP-MCF-7/S, a breast cancer parental sensitive cell line stably expressing green fluorescent protein (GFP), was constructed by recombinant lentiviral vector with GFP. Then the resistance experiment of cells and the experiment of resistance transfer by exosomes were designed to observe the phenomenon of cell-to-cell drug-resistance transfer.

RESULTSSimilar to the breast cancer parental sensitive cells (MCF-7/S), the breast cancer resistant sublines could secrete exosomes, which exhibited round or elliptic shape ranging from 30 to 100 nm in diameter with intact membrane, and only expressed the protein marker of exosomes, Tsg101, did not express the endoplasmic reticulum marker calnexin. After MCF-7/S, MCF-7/DOC and MCF-7/ADM cells we cocultured with GFP-MCF-7/S cells for 72 h, there were no significant differences in the expression of fluorescence-labeled cells among the four groups. When treated by the drug ADM or DOC for 24 hours, the MCF-7/DOC+GFP-MCF-7/S group was in favor of a significant higher survival rate of fluorescence-labeled cells compared with the MCF-7/S+GFP-MCF-7/S group (65.5% vs. 25.5%, P < 0.001), and so did the MCF-7/ADM+GFP-MCF-7/S group (53.6% vs. 25.4%, P < 0.001). The exosomes extracted from MCF-7/S, MCF-7/DOC and MCF-7/ADM cells were cultured with the GFP-MCF-7/S cells for 48 h. Among these groups, no significant differences in the expression of fluorescence-labeled cells were found. After treated by the drug ADM or DOC for 24 hours, the exosomes extracted from MCF-7/DOC+GFP-MCF-7/S group was associated with a significant higher survival rate of fluorescence-labeled cells compared with the exosomes extracted from MCF-7/S+GFP-MCF-7/S group (59.9% vs. 32.4%, P < 0.001), and so did the exosomes extracted from the MCF-7/ADM)+GFP-MCF-7/S group (58.3% vs. 27.2%, P < 0.001).

CONCLUSIONOur results suggest that drug-resistance can be transferred between breast cancer cells, and exosomes are probably the transporter of the drug resistance.

Antibiotics, Antineoplastic ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Survival ; Coculture Techniques ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Endosomal Sorting Complexes Required for Transport ; metabolism ; Exosomes ; metabolism ; pathology ; Green Fluorescent Proteins ; metabolism ; Humans ; MCF-7 Cells ; pathology ; Taxoids ; pharmacology ; Transcription Factors ; metabolism