Objective To investigate the expression level and clinical significance of cyclic citrullinated peptide antigen-specific T cells(CCP/AST)in synovial fluid and synovial tissue of rheumatoid arthritis(RA)patients.Methods A total of 128 RA patients in Shijiazhuang Hospital of Traditional Chinese Medicine from January to December 2021 were selected as the RA group,and 50 patients who needed arthroscopy for joint pain in the hospital during the same period were selected as the control group.Among the RA group,there were 46 cases in the mild group,52 cases in the moderate group,and 30 cases in the severe group.The protein expression levels of rheumatoid factors(RF)and anticitrullinated protein antibodies(ACPA)in synovial tissues of the subjects in each group were analyzed by Western blot.The frequency of CCP/AST in the synovial fluid of the subjects was analyzed by flow cytometry.The intensity of the staining of CCP/AST in synovial tissues was observed by double immunofluorescence staining/laser confocal scanning.Pearson correlation analysis was used to assess the correlation between the CCP/AST expression of synovial fluid and synovial tissue and RF and ACPA.Logistic regression was used to analyze the risk factors for the development of rheumatoid arthritis.Results In the order of control,mild,moderate and severe groups,RF(1.01±0.01,1.53±0.03,2.01±0.08,2.66±0.12 kDa)and ACPA proteins(1.03±0.01,1.61±0.03,2.04±0.10,2.59±0.13 kDa)in synovial tissues of patients were sequentially elevated,and the differences were all statistically significant(F=14.207,12.446,all P＜0.05).The expression of CCP/AST in synovial fluid of patients in the control,mild,moderate and severe groups was increased sequentially(8.26%±1.68%,22.46%±3.28%,33.58%±4.37%,46.15%±5.44%),and the difference was statistically significant(F=25.306,P＜0.05).Meanwhile,the intensity of CCP/AST staining in synovial tissues of patients in the control,mild,moderate and severe groups was also increased sequentially(1.05±0.26,1.35±0.89,2.04±0.56,2.78±0.15 score),and the difference was statistically significant(F=70.67,P＜0.05).The expression of CCP/AST in the synovial fluid and synovial tissues of patients with RA was positively correlated with RF(r=0.861,0.934,all P＜0.05)and ACPA in synovial fluid and synovial tissue(r=0.854,0.913,all P＜0.05).Logistic regression analysis showed that hypertension(OR=3.241,95%CI:1.491～6.752),diabetes mellitus(OR=2.565,95%CI:1.126～5.813),synovial fluid(OR=4.450,95%CI:1.652～11.622),and CCP/AST expression in synovial tissues(OR=5.629,95%CI:2.474～12.390)were independent risk factors for the development of RA(P＜0.05).Conclusion CCP/AST showed high expression in synovial fluid and synovial tissue of RA patients and related to disease activity and joint destruction,which can be used to assess the clinical joint mobility and bone destruction degree in such patients.

Objective To examine the differential expression of plasma circRNA in individuals with type 2 diabetes mellitus(T2DM)and to elucidate the potential role of circRNA in the pathogenesis and progression of T2DM.Methods A total of 33 newly diagnosed T2DM patients who were hospitalized in the Department of Endocrinology of Heze Municipal Hospital and 33 healthy subjects with normal glucose tolerance(NC)were enrolled in this study from March 2022 to March 2023.Three subjects with T2DM and 3 with NC were randomly selected from study population and underwent high-throughput sequencing to identify differentially expressed circRNA.Six circRNA with significant differences were selected,and validated in the remaining study population using Real-Time Quantitative Polymerase Chain Reaction(RT-qPCR).Bioinformatics analyses were conducted on the differentially expressed circRNA-associated genes,and their interaction with microRNA(miRNA)was predicted.Results Microarray analysis revealed 166 significantly differentially expressed circRNA(FC≥2,P<0.05)in the T2DM group compared with NC group.Among them,137 were up-regulated and 29 were down-regulated.RT-qPCR validation of six circRNA showed that the expression level of hsa_circ_0000705 was significantly higher,while the expression levels of hsa_circ_0005362 and hsa_circ_0042839 were significantly lower in T2DM group,consistent with the microarray results.However,hsa_circ_0117392,hsa_circ_0008311,and hsa_circ_0087641 showed no significant changes.Conclusion Differentially expressed circRNA are present in T2DM patients.Hsa_circ_0005362 was significantly down-regulated and may be involved in the development of T2DM through the regulation of related signaling pathways by targeting miR-128-1-5p.

AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

Objective To explore the practice and significance of the new course of"Enhanced Recovery after Sur-gery(ERAS)and Perioperative Management"for graduate students under multidisciplinary cooperation.Methods The Department of Anesthesiology collaborated with the Department of Clinical Nutrition,Department of Geriatrics and six related surgical departments to develop a course of 30 credit hours on"ERAS and Perioperative Manage-ment"in Peking Union Medical College Hospital.Researchers analyzed the teaching effectiveness of the course by collecting survey questionnaires and evaluating scheme report of ERAS case.Results Researchers found that ten graduates joined this course and they believed that learning improved their understanding of ERAS related knowl-edge,such as preoperative nutrition and functional state optimization,intraoperative volume and temperature man-agement,prevention of postoperative nausea and vomiting,and perioperative pain management.Students had high satisfaction with the course and believed that it would help improve their clinical literacy.Conclusions The new course of"ERAS and Perioperative Management"for graduates may support capacity building in terms of clinical logic and thinking about ERAS and promotion of skills for perioperative management.Our experience of graduates′training with"Enhanced Recovery after Surgery and Perioperative Management"course can be shared by other trainers of health institution of China.

  Objective  To explore the mechanism of Wnt5a on keratinocyte involved in the peripheral sensitization of complex regional pain syndrome type-Ⅰ (CRPS-Ⅰ) by regulating the expression of MMP9, and search for potential therapeutic strategies.  Methods  Cultured HaCaT cells were treated with oxygen glucose deprivation/re-oxygenation (OGD/R). The early stage of mitochondrial damage and membrane potential changes after OGD/R and the effects of Box5 (Wnt5a inhibitor) at different concentrations (20 μmol/L, 40 μmol/L) on MMP9 were explored. Adult male Sprague-Dawley rats were divided into Control group(n=8), CPIP group (n=8), Box5 (20) group (n=8) and Box5 (40) group (n=8). The rat chronic post-ischemia pain (CPIP) model was established to mimic the pathophysiological process of CRPS-Ⅰ. Box5 (20) group and Box5 (40) group were treated with intraplantar injection of 20 μmol/L and 40 μmol/L Box5 100 μL, respectively. The changes of mechanical withdrawal threshold and thermal withdrawal latency were measured within two weeks, and the skin inflammatory infiltration and keratosis were observed by HE staining. The expression of MMP9 was observed by immunofluorescence, and the levels of IL-1β and TNF-α in dorsal root ganglion of different groups were detected by ELISA.  Results  Vitro experiment: After OGD/R treatment, the mitochondrial atrophy was observed in OGD/R group under transmission electron microscope and the average fluorescence intensity of MMP9 was found to increase significantly (P<0.001). Compared with Control group, the mitochondrial membrane potential in OGD/R group decreased significantly by JC-1 detection (P=0.027). Compared with OGD/R group, only Box5 (40) group had a statistically significant increase in mitochondrial membrane potential (P=0.046). Animal experiment: Behavioral tests showed that the mechanical pain threshold and thermal pain threshold of CPIP group were significantly decreased at each time point (D1, D2, D4, D10, D14) (all P<0.05). HE staining indicated that there was a large-scale infiltration of inflammatory cell in the dermis and excessive keratosis in the epidermis, and the thickness of stratum granulosum and stratum spinosum increased significantly (P < 0.001). Immunofluorescence analysis showed that the expression of MMP9 in CPIP group was significantly increased (P<0.001). Compared with CPIP group, the fluorescence intensity of MMP9 in Box5 (20) group (P=0.002) and Box5 (40) group (P<0.001) were significantly decreased. ELISA results showed that the concentrations of IL-1β (P=0.048) and TNF-α (P=0.002) in CPIP group were significantly increased. Compared with CPIP group, the concentrations of IL-1β (P=0.047) and TNF-α (P=0.047) were significantly decreased in Box5 (40) group.  Conclusions  Peripheral ischemia reperfusion injury leads to overexpression of MMP9 on keratinocytes, resulting in CRPS-Ⅰ peripheral sensitization. Targeted inhibition of Wnt5a/MMP9 pathway can reverse pain behavior in rat model of CPIP, thus providing a strategy for clinical treatment of chronic pain.

  Objective  To elucidate whether coffee consumption and caffeine intake was associated with various subtypes of pain based on extensive data from publicly accessible databases.  Methods  The information was extracted from three cycles of the American National Health and Nutrition Examination Survey (1999—2000, 2001—2002, 2003—2004), encompassing data on coffee consumption, pain information, and 11 covariates (including age, gender, race, etc.). Multinomial logistic regression in three models were utilized for analysis.  Results  A total of 13 428 participants were included in this study, with a mean age of (49.79±19.06)years and a male-to-female ratio of 0.9∶1. Daily coffee intake: non-drinker 7794(58.0%), > 0-2 cups 2077(15.5%), > 2 cups 3557(26.5%); daily caffeine intake: without intake 7794(58.0%), > 0-200 mg 3152(23.5%), > 200 mg 2482(18.5%); pain situation: no pain or pain duration < 24 h 10 202(76.0%), acute pain 910(6.8%), subacute pain 369(2.7%), chronic pain 1947(14.5%). After weighting, 13 428 participants were expected to represent 190 million(190 709 157) U.S. citizens aged ≥20 years, and the overall prevalence of acute, subacute, and chronic pain in the U.S. population during that period was estimated to be 8%, 3%, and 16%, respectively. Without adjusting for covariates, individuals who consumed more than 2 cups of coffee or 200 mg of caffeine per day exhibited an elevated risk of chronic pain compared to non-coffee/caffeine drinkers, with an odds ratio of 1.354(95% CI: 1.187-1.544) and 1.372(95% CI: 1.185-1.587), respectively. After adjusting for partial covariates including age, sex, and race, individuals who consumed more than 2 cups of coffee or more than 200 mg of caffeine per day still demonstrated an increased risk of chronic pain with an odds ratio of 1.243(95% CI: 1.083-1.427) and 1.249 (95% CI: 1.072-1.456), respectively. However, after all covariates were adjusted, there was no significant association between coffee/caffeine consumption and chronic pain. Furthermore, the number of cups of coffee consumed or caffeine intake showed no significant correlation with acute and subacute pain.  Conclusions  Compared with nondrinkers, heavy daily coffee drinkers may be more likely to have chronic pain, but it is affected by multiple factors. Basic research and prospective clinical studies are needed to further determine the causality in this association.

Objective:To develop college students' proactive aggression questionnaire (CPAQ) and test its reliability and validity.Methods:From March 2023 to April 2024, a questionnaire survey was conducted among 1 552 college students(618 individuals in Sample 1, 783 individuals in Sample 2, 151 individuals in Sample 3 (retested after a 6-month interval), and 49 individuals in Sample 4 (randomly selected from Sample 3)).The reliability and validity of CPAQ were assessed using SPSS 24.0 and Mplus 8.3 software through item analysis, exploratory factor analysis, confirmatory factor analysis, internal consistency reliability, test-retest reliability, compatibility validity, discriminant validity, and empirical validity.Results:The results of the project analysis showed that the 33 items in the CPAQ were significantly correlated with the total score( r=0.25-0.78, P<0.05), and item scores between the high and low group were significantly different (all P<0.001). Exploratory factor analysis retained 28 items, which belonged to three dimensions of proactive aggression (instrumental motivation, moral inhibition, and moral disengagement). The results of confirmatory factor analysis showed that the three-dimensional model of the questionnaire was well fitted ( χ2/ df=3.25, CFI=0.96, TLI=0.95, RMSEA=0.05, SRMR=0.06). The Cronbach's α coefficients for the total score of CPAQ and its sub dimensions were 0.93, 0.95, 0.89 and 0.75, respectively(all P<0.05). The test-retest reliability was 0.64, 0.63, 0.67 and 0.60, respectively(all P<0.01). In the compatibility validity test, the instrumental motivation dimension score was positively correlated with the proactive aggression dimension score of reactive-proactive aggression questionnaire(RPQ)( r=0.50, P<0.05), while moral inhibition dimension was negatively correlated with empathy and guilt scores( r=-0.30, -0.39, P<0.05). The dimension of moral disengagement was positively correlated with the score of the moral disengagement scale( r=0.58, P<0.05). In the discriminant validity test, the correlation of CAPQ and RPQ reactive aggression dimension score was not significant( r=0.08, P=0.16). In the criterion related validity test, the correlation coefficients between the score of CAPQ and each calibration questionnaire and scale were 0.70-0.83. In the empirical validity test, there was a significant difference in the different CPAQ score groups for proactive aggressive behavior(high group: (1.16±0.18), low group: (1.04±0.08), t=2.60, P<0.05). Conclusion:CPAQ has good discrimination, reliability, and validity, which could be used as a tool to measure proactive aggressive behavior among college students.

To improve the current situation of multiple preoperative visits and evaluations for elderly patients and other patients with complex conditions, in December 2022, Peking Union Medical College Hospital established preoperative multidisciplinary evaluation clinic (shorted as joint clinic). The joint clinic established a multidisciplinary team, clarified service targets, and developed standardized clinic workflows to provide patients with a " one-stop" preoperative assessment(physical fitness assessment, nutritional assessment, and frailty assessment, etc.), nutritional optimization intervention, and prerehabilitation education and guidance services. This practice strengthened preoperative risk management, improved preoperative assessment efficiency, and ensured the safety of patients during the perioperative period. As of September 2023, the joint clinic had received a total of 128 patients, of which 86 underwent surgery after preoperative evaluation and prehabilitation optimization. The obesity rate, smoking rate, and number of frailty cases of these patients had decreased from 13.96%, 11.63%, and 18 at the time of visit to 9.30%, 4.65%, and 14 on the day before surgery, respectively. They had recovered well after surgery. This practice had improved the preoperative status of patients and created conditions for high-risk patients to undergo surgery smoothly, so as to provide references for other hospitals to carry out multidisciplinary collaborative preoperative evaluation works.

Objective:To evaluate the value of enhanced CT radiomics feature model for predicting 5-year overall survival (OS) of esophageal squamous cell carcinoma patients after radiotherapy.Methods:Clinical data of 218 patients with esophageal squamous cell carcinoma treated with radical chemoradiotherapy in the Fourth Hospital of Hebei Medical University from July 2016 to December 2017 were retrospectively analyzed. Patients were randomly divided into the training group ( n=153) or a validation group ( n=65) at a 7 vs. 3 ratio. Enhanced CT radiomics features were extracted. The data in the training group was used to construct the prediction model, and the data in the validation group were utilized to validate the efficiency of this model for predicting the 5-year OS of patients. The predictive performance of this model was assessed by the receiver operating characteristic (ROC) curve, consistency index (C-index), and decision curve analysis (DCA). Results:The 1-, 3-, 5-year OS rates were 67.0%, 33.4%, 24.9%. Five radiomic features were selected from extracted features in the training group to construct the radiomic signature (RS) for predicting 5-year OS. The area under the ROC curve (AUC) was 0.760 in the training group and 0.707 in the validation group, and the C-index was 0.680 and 0.684, respectively. The radiomics nomogram, which incorporated the RS with clinical risk factors, were established to predict the 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy. The AUC was 0.782 in the training group and 0.751 in the validation group, and the C-index was 0.708 and 0.688, respectively. According to the optimal cutoff of the model, all patients were divided into the high risk and low risk groups. The 1-, 3-, 5-year OS rates were 86.5%, 65.4%, 28.9% in the low risk group, and 58.4%, 17.8%, 5.9% in the high risk group, and the differences were statistically significant (all P<0.001). Similar conclusions were obtained in the validation group (all P<0.001). Conclusion:Enhanced CT radiomics features can be utilized to construct the prediction model for 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy, which can be applied in clinical practice.