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.

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.

Objective:To explore the effect of virtual reality (VR) on the emergency management of pediatric anesthesia.Methods:Four kinds of perioperative critical events were selected as VR training content, and the training objects were 60 residents who took part in the standardized residency training in Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine. Through theoretical examination and questionnaire survey, the training effect and the anxiety of residents after critical events were evaluated. The data were input into Graphpad Prism 5 software, and the quantitative data conforming to normal distribution were expressed as (mean ± standard deviation), and compared by nonparametric test and t test of two independent samples between groups. Qualitative data were expressed in terms of rate, and the 2× k trend chi-square test was used to compare the scores of the two groups. Results:All the residents took part in the theoretical assessment of the management of pediatric anesthesia emergencies. Compared with the offline theoretical teaching, the average scores of the students who underwent VR training were higher, and the incidence of anxiety was significantly reduced.Conclusion:VR simulation teaching in the department of anesthesiology can fully arouse the enthusiasm of residents and make them overcome the fear of dealing with pediatric anesthesia emergencies.

Antibiotics can not only combine with specific targets, but also induce a cascade of re-active oxygen species ( ROS) in bacteria. Antioxidant defense system plays an important role in scavenging ROS and repairing injury against oxidative stress. However, the mechanism of ROS accumulation in bacteria and the action of ROS are very complicated. Therefore, this paper reviewed the mechanisms of bacterial re-sponding to oxidative stress in the existence of antibiotics. In addition, we analyzed the main problems lying in the current study and the issues needing further consideration.

Objective To investigate the association between the tumor necrosis factor (TNF)-α-308 G＞A polymorphism and risk of non-Hodgkin lymphoma (NHL).Methods PubMed,CNKI and Wanfang dataknowledge service platform were searched to obtain relevant literature by using the following terms:lymphoma and (tumor necrosis factor or TNF) and (polymorphism or SNP or variant or mutation).Overall results were combined by using fixed effect model or random effect model.Publication bias was evaluated by using the Begg funnel plot and Egger test.Results Fifteen eligible studies were identified,including 9 738 NHL cases and 10 854 controls.The results of the overall meta-analysis showed that the TNF-α-308 AA genotype was associated with increased risk of NHL in two genetic models (AA vs.GG:OR =1.55,95 ％ CI 1.30-1.86,I2 =42.4 ％;AA vs.AG+GG:OR =1.53,95 ％ CI 1.27-1.83,I2 =41.8％).Stratified by ethnicity,TNF-α-308 A allele was associated with an increased NHL risk in Caucasians (A vs.G;AA vs.GG;AG vs.GG;AA vs.AG+GG;AA+AG vs.GG) but a decreased risk in Asians (A vs.G;AG vs.GG;AA+AG vs.GG).Conclusion The TNF-o-308 G＞A polymorphism is associated with the risk of NHL.

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 diagnostic value of fetal echocardiography in total anomalous pulmonary venous connection (TAPVC),and to analyze the reasons ofmisdiagnosis so as to improve accuracy of prenatal diagnosis.Materials and Methods The prenatal echocardiographic data of 24 cases of TAPVC confirmed by postnatal echocardiography and prenatal MRI from October 2001 to December 2015 in Children's Hospital Affiliated to Nanjing Medical University and Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed.Results In 24 cases,there were 14 fetuses of supracardiac type,7 cases of intracardiac type,2 cases of infracardiac type,and 1 case of mixed type.15 fetuses had TAPVC only,whereas 9 cases were associated with other cardiovascular anomalies,most commonly including bilateral right atria,single atrium,single ventricle,common atrioventricular valve and pulmonary stenosis.On 4-chamber views,the common sonographic sign was absent of pulmonary venous return to the left atrium in 24 cases (100.0％),and the presence of venous confluence between left atrium and descending aorta was observed in 22 cases (91.7％).In all 24 cases,1 case was missed diagnosis,and 3 cases were misdiagnosed as persistent left superior vena cava,common pulmonary vein atresia and patent left atrial cardinal vein.Conclusion TAPVC can be accurately diagnosed by fetal echocardiography,but it is prone to be misdiagnosed.

Ultrasonography has grown rapidly and gained widespread acceptance in various fields.It has become a favored diagnostic imaging tool for its non-invasive,non-ionizing radiation,fast,convenient and portable.This article described briefly the application of ultrasound in vascular and its related diseases.

Objective To explore the ultrasound imaging and the clinical analysis of eosinophilic cystitis in children and to improve the understanding of this very rare clinical disease.Methods The ultrasound imaging of 9 patients who were diagnosed as eosinophilic cystitis in Nanjing Children's Hospital Affiliated to Nanjing Medical University from Jul.2007 to May 2013 were analyzed retrospectively,and the relevant literatures were reviewed.Results The ultrasound imaging of the 9 patients were described as follows:4 cases showed a diffuse thickening bladder wall,2 cases showed a localized mass-like thickening bladder wall,and 3 cases showed a markedly thickening anterior bladder wall and bilateral bladder wall.Laboratory studies showed that all the patients were presented with eosinophilia.Six patients underwent cystoscopy that showed an erythematous,and velvety appearance of the bladder mucosa.Histopathology disclosed a bladder mucosal tissue with dense interstitial eosinophilic infiltration consistent with eosinophilic cystitis.Three patients had clinical resolution under the treatment of anti-infections and urine alkalinization.Other 6 patients received prednisone at 0.5-1.0 mg/kg and an antihistamine treatment.Prednisone was eventually tapered off after 2-week reemission.Regular follow-up by urinary bladder ultrasound and urine routine did not show any disease recurrence in 9 children.Conclusions The combination of bladder wall thickening and peripheral eosinophilia may suggest the likely diagnosis of eosinophilic cystitis.Cystoscopy with bladder biopsy is the most important step in the diagnosis of eosinophilic cystitis.Anti-histamines and corticosteroids can be used as the primary management and have good results.