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.

Inflammatory bowel disease (IBD) is a chronic and nonspecific disease affected by both genetic and environmental factors. Ecological and social environmental factors, including air pollutants, heavy metals, industrial pollutants and organic pollutants, diet, and lifestyle, influence the occurrence and development of IBD and regulate IBD gene expression through epigenetics and gut microbiota. This article summarizes the role of environmental factors in IBD and explores the ways in which they influence the regulation of gene expression.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with unclear etiology. Existing studies indicate that diet plays an important role in both the pathogenesis and prognosis of IBD. This review summarizes clinical evidence regarding the association between diet and the development of IBD, analyze the current nutritional status of the IBD population at the prognosis level and underlying mechanisms of dietary interventions in disease management, and explores the application of precision nutrition in personalized care. The review ultimately aims to provide guidance for developing more precise and personalized dietary management strategies for IBD patients.

AIM:To identify surrogate clinical bio-markers for profiling the eosinophilic status of an individual patient over induced sputum analysis.METHODS:We conducted a cross-sectional study on 100 asthmatic patients whose induced sputum was successfully collected.Subjects were further classified into either EA or NEA based on whether the percentage of sputum eosinophil count(SEC％)was≥3％.Demographic and clinical data were col-lected,including basic information,routine blood tests,lung function tests,bronchodilator reversibili-ty tests,fractional exhaled nitric oxide(FeNO),the Asthma Control Test(ACT)and the Asthma Control Questionnaire(ACQ).All variables significantly asso-ciated with EA were candidates for multivariate lo-gistic regression analysis.A scoring system present-ed as a nomogram for the prediction of EA was de-veloped.RESULTS:In the univariate analysis,com-pared with NEA subjects,those with EA were of older age and had worse asthma control and lung function in addition to higher values of blood eosin-ophils,serum IgE and FeNO.Multivariable logistic regression analysis revealed that age,FeNOx serum IgE and blood eosinophil count(BEC)were identi-fied as independent risk factors for eosinophilic asthma,which were all included in the nomogram.CONCLUSION:A combination assessment including age,FeNOx serum IgE and BEC could be applicable to clinicians in identifying eosinophilic asthma and is easier,faster,more inexpensive and more readily available than the induced sputum test.

Inflammatory bowel disease (IBD) is a chronic and nonspecific disease affected by both genetic and environmental factors. Ecological and social environmental factors, including air pollutants, heavy metals, industrial pollutants and organic pollutants, diet, and lifestyle, influence the occurrence and development of IBD and regulate IBD gene expression through epigenetics and gut microbiota. This article summarizes the role of environmental factors in IBD and explores the ways in which they influence the regulation of gene expression.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with unclear etiology. Existing studies indicate that diet plays an important role in both the pathogenesis and prognosis of IBD. This review summarizes clinical evidence regarding the association between diet and the development of IBD, analyze the current nutritional status of the IBD population at the prognosis level and underlying mechanisms of dietary interventions in disease management, and explores the application of precision nutrition in personalized care. The review ultimately aims to provide guidance for developing more precise and personalized dietary management strategies for IBD patients.

AIM:To identify surrogate clinical bio-markers for profiling the eosinophilic status of an individual patient over induced sputum analysis.METHODS:We conducted a cross-sectional study on 100 asthmatic patients whose induced sputum was successfully collected.Subjects were further classified into either EA or NEA based on whether the percentage of sputum eosinophil count(SEC％)was≥3％.Demographic and clinical data were col-lected,including basic information,routine blood tests,lung function tests,bronchodilator reversibili-ty tests,fractional exhaled nitric oxide(FeNO),the Asthma Control Test(ACT)and the Asthma Control Questionnaire(ACQ).All variables significantly asso-ciated with EA were candidates for multivariate lo-gistic regression analysis.A scoring system present-ed as a nomogram for the prediction of EA was de-veloped.RESULTS:In the univariate analysis,com-pared with NEA subjects,those with EA were of older age and had worse asthma control and lung function in addition to higher values of blood eosin-ophils,serum IgE and FeNO.Multivariable logistic regression analysis revealed that age,FeNOx serum IgE and blood eosinophil count(BEC)were identi-fied as independent risk factors for eosinophilic asthma,which were all included in the nomogram.CONCLUSION:A combination assessment including age,FeNOx serum IgE and BEC could be applicable to clinicians in identifying eosinophilic asthma and is easier,faster,more inexpensive and more readily available than the induced sputum test.

Objective:To study the overall training effect of segmented training model on key fiberoptic bronchoscopy techniques for anesthesiology residents and the influence of key technique training order on the training effect.Methods:Different fiberoptic bronchoscopy simulators were used for specialized training in different key techniques of fiberoptic operation. To examine the effect of key technique learning order on the teaching effect, 40 anesthesiology residents who participated in fiberscope simulation training at Ruijin Hospital, Shanghai Jiaotong University School of Medicine between November 2022 and March 2023 were selected for this study. They were randomly divided into two groups (Group S and Group M) using a numerical table method. The teaching was completed using two orders of key techniques. The operation time, operation quality score, and theoretical knowledge mastery score of the two groups were recorded to compare the effect of key technique learning order on the mastery of fiberoptic skills. SPSS 29.0 statistical software was used for data analysis. Measurement data that conformed to normal distribution were expressed as mean ± standard deviation, and the independent samples t-test or Fisher's exact test were used for comparison between groups. The chi-square test was used for comparison of enumeration data. Results:After segmented training in each key technique, both groups of trainees were able to shorten the operation time of the corresponding key technique [SM simulator operation time (132.25±14.69) s vs. (49.80±4.46) s in group S, P<0.01; M simulator operation time (82.30±11.60) s vs. (57.10±6.77) s in group S, P<0.01; SM simulator operation time (83.10±10.62) s vs. (52.10±5.20) s in group M, P<0.01; M simulator operation time (132.25±14.69) s vs. (55.40±5.91) s in group M, P<0.01)]. Moreover, both groups showed a reduced number of wall touches [SM simulator wall touches (3.35±0.93) times vs. (0.65±0.49) times in group S, P<0.01; M simulator wall touches (2.50±1.05) times vs. (0.70±0.80) times in group S, P<0.01; SM simulator wall touches (1.55±1.15) times vs. (0.40±0.50) times in group M, P<0.01; M simulator wall touches (5.90±1.29) times vs. (1.10±0.79) times in group M, P<0.01]. There were no significant differences between the two groups in the performance score of fiberoptic-guided tracheal intubation after training [(92.50±5.97) points vs. (91.75±5.45) points] and in the lung segment localization time [(23.15±4.39) s, (21.40±4.84) s, (22.85±4.42) s vs. (22.75±5.11) s, (21.00±5.40) s, (21.50±5.10) s]. Conclusions:Segmented training on key fiberoptic bronchoscopy techniques is an effective model of fiberscope training for anesthesiology residents, and the order of training key techniques does not affect the effectiveness of training.

BACKGROUND: As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment. METHODS: Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses. RESULTS: In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002). CONCLUSIONS The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.
Humans ; B7-H1 Antigen/antagonists & inhibitors* ; Drug Therapy, Combination ; Immune Checkpoint Inhibitors/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Breast Neoplasms/drug therapy*

Objective: To investigate the association of sleep quality, depressive symptoms and their interaction with non suicidal self injury (NSSI) among rural middle school students, so as to provide a reference for early prevention and control of NSSI among rural middle school students. Methods: A multi stage cluster sampling method was used to randomly select four rural middle schools in Xuzhou, Jiangsu Province. A total of 1 723 middle school students were investigated according to the principle of grade stratification and class random selection. Paper questionnaires (including demographic factors, Non Suicidal Self Injury Short Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnare-9) were used to conduct the questionnaire survey. Logistic regression model was used to analyze the association of sleep quality, depressive symptoms and their interaction with NSSI among rural middle school students. Results: Totally 30.5% of middle school students had NSSI. Univariate results showed that girls (33.0%) had a higher incidence of NSSI than boys(27.3%), and those with sleep disorders and depressive symptoms had a higher incidence of NSSI, which was 46.8%, 43.6%. The results of multivariate Logistic regression showed that the risk of NSSI in students with sleep disorder was 1.80 times that in those without sleep disorder( OR 95%CI=1.42-2.28, P <0.01). The risk of NSSI in students with depressive symptoms was 3.32 times higher than that in those without depressive symptoms( OR 95%CI=2.60-4.24, P <0.01). The interaction results showed that there was additive interaction between sleep disturbance and depressive symptoms on the occurrence of NSSI behavior in rural middle school students, and the relative excess risk, attributable proportion and synergy index were 1.80, 0.30 and 1.57, respectively. Conclusion Sleep disorder and depressive symptoms are risk factors for NSSI among rural middle school students, and there is additive interaction between them.