BACKGROUND: Restriction is a reliable means in the study of psychological stress, and restriction stress can suppress cellular immunity of T lymphocytes through hypothalamus-pituitary-adrenal axis.OBJECTIVE: To investigate the changes of Th1/Th2 balance due to restriction stress in cancer-loaded rats and the growth of cancer so as to explore the effect of psychological stress on cancer cells.DESIGN:Case control study based on experimental animal as subjects.SETTING: Teaching and Research Department of Microbiology and Immunology of Beijing University of Traditional Chinese Medical.MATERIALS: This study was carried out in the Immunology Laboratory of Beijing Traditional Chinese Medical University. Kunming rats of 6-8weeks old were selected. They were raised for 3 days before experiment to adapt to the environment and numbered according to their weight. Rats with the highest and lowest body weight were excluded, and the rest were randomly divided into 4 groups of 16 rats (8 male rats and 8 female rats)weighing 18 to 20 g.METHODS: S180 cancer cells were collected at 7 days of celiac subculture and rinsed with normal saline before made into cell suspensions of 1×1010 L-1 with RPMI 1640 medium. Rats were given subcutaneous injection of 0.2 mL cell suspension at the right axilla in cancer group and cancer-combined restriction group. Meanwhile, the same dosage of normal saline was used instead in normal control group and pure restriction group in the same way. After injection, movements of rats in pure restriction group and cancer-combined restriction group were restricted in specially-made tubes for 8 hours a day. Ten days later rats were killed to remove the tumor and thymus which were then weighed for calculating the thymus index. MTT colorimetry and mitogen-activated immunoblast method were used to examine the proliferation of spleen T lymphocytes and the production of Thl-type cytokines, such as interleukin-2(IL-2), interferon-γ (IFN-γ); meanwhile,ELISA technique was used to detect the level of serum Th2-type cytokines,such as interleukin-4(IL-4) and interleukin-10(IL-10).MAIN OUTCOME MEASURES: Primary outcomes: effect of restriction stress on T lymphocyte' production of IL-2 and interferon-γ, and on IL-4and IL-10 as well as the effect in promoting the cancer growth in cancer-loaded rats. Secondary outcomes: effect of restriction stress on T-lymphocyte proliferation and thymus index.RESULTS: Restriction stress significantly increased the cancer weight and decreased thymus index and the proliferation of spleen T lymphocytes. Meanwhile, IL-2 and IFN-γ produced by spleen cells also decreased, with serum IL-4 and IL-10 level obviously increased in cancer-loaded rats.CONCLUSION:The cellular immunity of cancer-loaded rats was obviously suppressed due to restriction stress, which was presented by decreased Thl-type cytokine production and increased Th2-type cytokine production,resulting in Thl/Th2 cytokine imbalance towards Th2. It may be the important mechanism of its promoting effect on the growth of cancer.

Objective To explore the effect of orthopedic sub-discipline rotation mode in the postgraduate orthopaedic education. Meth-ods Randomly selected orthopaedic postgraduate students from grade 2011 and grade 2012 (30 students each grade). Students from grade 2011 went through the traditional teaching mode,and students from grade 2012 adopted 2 months of rotation in each sub-discipline. The clini-cal examination results and teaching satisfaction of the two groups were analyzed. Results The clinical examination results and teaching sat-isfaction of students from the two grades showed statistically differences (P<0. 05). Conclusion Orthopaedic sub-discipline rotation teach-ing mode improved the postgraduates in different ways such as orthopaedic theoretical knowledge, clinical skills, case analysis and so on. Meanwhile,the new teaching mode can get students more satisfied.

Objective To compare the incidence of secondary surgical procedures after cervical disc arthroplasty vs anterior cervical discectomy with fusion in patients treated for symptomatic single level cervical spondylosis.Methods An online search of Pubmed, Medline, Ovid, Embase, Cochrane Library, CBM database, Wanfang data and VIP database were searched for prospective randomized controlled trial of cervical disc arthroplasty versus anterior cervical discectomy with fusion in incidence of secondary surgical procedures.Data were collected and extracted by two reviewers independently.Risk of bias was assessed using the criteria of Cochrane Reviews Handbook 5.1.0.Review Manager 5.2 software system was used to evaluate the data for Meta analysis.Results A total of 12 trials were included.Six of them were short-term follow up (two years).The 6 other trials were mid-and long-term follow up (mean 5.8 years).There are 4 trials with low risk of bias, 7 trials with moderate risk of bias, and 1 trial with high risk of bias.The results of meta-analysis showed there was no statistical difference in reoperation rate of adjacent level between the two groups at two years follow-up;however, the reoperation rate of non-fusion group was significantly lower in the non-fusion group compared with fusion group at mid-and long-term follow-up.The incidence of secondary surgical procedures at index level was higher in fusion group than in non-fusion group.No statistical difference was found between the two groups in using ‘ removal’ for secondary surgical procedure at two years follow-up;however, the rate of non-fusion group was significantly lower than fusion group at mid-and long-term follow-up.Conclusion Cervical disc arthroplasty was partly superior to anterior cervical discectomy with fusion in avoiding secondary surgical procedures of adjacent levels.However, non-fusion surgery doesn't have any advantages in short time (two years) follow up.Reducing the incidence of pseudarthrosis was an effective way to decrease the incidence of secondary surgery procedures in index level.

Objective:To investigate the application value of CT and MRI imageomics based on machine learning method in the diagnosis of pancreatic cancer.Methods:The clinical data of 62 patients with surgically resected and pathologically confirmed pancreatic cancer, who underwent enhanced CT scan, MRI plain or enhanced scan in Shanghai General Hospital between January 2014 and December 2021 were collected. According to the chronological order of surgery, 49 patients from January 2014 to December 2020 were enrolled in the training set and 13 patients from January 2021 to December 2021 were enrolled in the validation set. 3D-slicer 4.8.1 software was used to draw the region of interest in each layer of CT and MRI images for cancerous and paracancerous tissue segment. Image features were extracted by Python and the optimal feature set from the training set data was obtained by using Lasso regression model. The machine learning decision tree model was constructed. The receiver operating characteristic curve(ROC) curve was drawn, and the area under the curve (AUC) was calculated to evaluate the value of these three kinds of imageomics models in the diagnosis of pancreatic cancer.Results:The 1 767 CT features and 1 674 MRI features were obtained from enhanced CT scan, MRI plain scan and enhanced MRI scan, respectively. For the differential diagnosis model of cancerous tissue and paracancerous tissue, the enhanced CT scan data model obtained the optimal feature set involving 6 features, the MRI plain scan model obtained the optimal feature set involving 16 features, and the enhanced MRI scan model obtained the optimal feature set involving 15 features. The diagnostic model based on enhanced CT scan had an AUC of 0.98 in the training set and 1 in the verification group. The AUC of the MRI plain scan and enhanced MRI scan models in both the training set and the validation set was 1. The specificity and sensitivity of machine learning decision tree model based on the three kinds of imageomics models in the diagnosis of cancerous tissue and paracancerous tissue were 100%. For the differential diagnosis model of splenic artery wrapping, the enhanced CT scan model didn′t obtain the optimal features and had no diagnostic efficacy. The MRI plain scan model and enhanced MRI scan model obtained the optimal feature set involving 5 and 4 features, respectively. The AUC of the MRI plain scan model in the training set and the validation set were 0.862 and 0.750, respectively, with diagnostic sensitivity of 93.8% and 50.0%, and specificity of 78.6% and 100%, respectively. The AUC of the enhanced MRI scan model in the training set and the validation set were 0.950 and 0.861, respectively, with diagnostic sensitivity of 90.0% and 93.6%, and specificity of 100% and 78.6%, respectively.Conclusions:Based on the radiomics of CT enhanced, MRI plain scan and enhanced MRI scan, the machine learning diagnostic model has an accuracy of more than 90% in differentiating pancreatic cancer from paracancerous tissue. For the differentiation of splenic artery wrapping in pancreatic cancer, the diagnostic model based on enhanced MRI scan haS the best diagnostic efficiency.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.