Objective:To explore the value of predicting new-onset heart failure events in patients with hypertrophic cardiomyopathy (HCM) using clinical and cardiac magnetic resonance (CMR) features based on machine learning algorithms.Methods:The study was a retrospective cohort study. Patients with a confirmed diagnosis of HCM who underwent CMR examinations at Beijing Anzhen Hospital from May 2017 to March 2021 were selected and randomly divided into the training set and the validation set in a ratio of 7∶3. Clinical data and CMR parameters (including conventional parameters and radiomics features) were collected. The endpoint events were heart failure hospitalization and heart failure death, with follow-up ending in January 2023. Features with high stability and P value<0.05 in univariate Cox regression analysis were selected. Subsequently, three machine learning algorithms—random forest, decision tree, and XGBoost—were used to build heart failure event prediction models in the training set. The model performance was then evaluated using the independent validation set, with the performance assessed based on the concordance index. Results:A total of 462 patients were included, with a median age of 51 (39, 62) years, of whom 332 (71.9%) were male. There were 323 patients in the training set and 139 in the validation set. The median follow-up time was 42 (28, 52) months. A total of 44 patients (9.5% (44/462)) experienced endpoint events (8 cases of heart failure death and 36 cases of heart failure hospitalization), with 31 events in the training set and 13 in the validation set. Univariate Cox regression analysis identified 39 radiomic features, 4 conventional CMR parameters (left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular ejection fraction, and late gadolinium enhancement ratio), and 1 clinical feature (history of non-sustained ventricular tachycardia) that could be included in the machine learning model. In the prediction models built with the training set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.966 (95% CI 0.813-0.995), 0.956 (95% CI 0.796-0.992), and 0.973 (95% CI 0.823-0.996), respectively. In the validation set, the concordance indices for the random forest, decision tree, and XGBoost models were 0.854 (95% CI 0.557-0.964), 0.706 (95% CI 0.399-0.896), and 0.703 (95%CI 0.408-0.890), respectively. Conclusion:Integrating clinical and CMR features of HCM patients through machine learning aids in predicting heart failure events, with the random forest model showing superior performance.

Objective To evaluate the long-term efficacy of tumor necrosis factor-α(TNF-α)inhibitor(TNFi)in the treatment of ankylosing spondylitis(AS)complicated with osteoporosis(OP)and the impact on bone metabolism,bone density,and inflammatory factors.Methods The data of 158 patients with AS and OP,who were admitted to Department of Rheumatology and Immunology of The First Affiliated Hospital of Naval Medical University(Second Military Medical University)from Jan.1,2010 to Dec.31,2017,were retrospectively collected.The patients were divided into bisphosphonate group(n=54),TNFi group(n=58),and TNFi+bisphosphonate group(n=46)according to the treatment methods.All patients were treated with calcium combined with calcitriol as the background treatment.After 5 years of treatment,Bath ankylosing spondylitis disease activity index(BASDAI)and Bath ankylosing spondylitis functional index(BASFI)scores were evaluated,and inflammatory indexes,bone metabolism markers,and bone mineral density were detected.Results After 5 years of treatment,the BASDAI and BASFI scores,erythrocyte sedimentation rate(ESR),C reactive protein(CRP),TNF-α,and interleukin-17A of the TNFi+bisphosphonate group and TNFi group were significantly lower than those before treatment(all P＜0.05);in the bisphosphonate group only ESR and CRP were significantly lower than those before treatment(both P＜0.05),and the other inflammatory indexes and BASDAI and BASFI scores showed no significant changes(all P＞0.05).The bone mineral density of the 3 groups after 5 years of treatment was significantly higher than that before treatment(all P＜0.05),and the bone mineral density of the TNFi+bisphosphonate group was significantly higher than that of the other 2 groups(both P＜0.05).After 5 years of treatment,the levels of parathyroid hormone(PTH),procollagen type 1 N-terminal propeptide(P1NP)and β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)in the TNFi+bisphosphonate group and bisphosphonate group were significantly decreased compared with those before treatment(all P＜0.05),while the levels of N-terminal midfragment of osteocalcin(N-MID)and 25-hydroxy-vitamin D(25VitD)were significantly increased(all P＜0.05);in the TNFi group only PTH and P1NP levels were significantly decreased(both P＜0.05),while β-CTX,N-MID and 25VitD levels showed no significant differences(all P＞0.05).Conclusion Long-term use of TNFi in patients with AS and OP can effectively reduce disease activity,improve physical function,decrease the level of inflammatory factors,alleviate abnormal bone metabolism,and increase bone mineral density;and the combined use of TNFi and bisphosphonates has better efficacy.

Objective:To explore the application effect of multidimensional intervention strategies based on sensitive risk indicators in patients with uterine fibroids complicated with climacteric syndrome.Methods:From October 2020 to October 2021, the convenient sampling method was used to select 120 patients with uterine fibroids complicated with climacteric syndrome from Affiliated Hospital of Jining Medical University as the research subjects. They were divided into the observation group and the control group using the random number table method, with 60 cases in each group. The control group received routine care, while the observation group implemented multidimensional intervention strategies based on sensitive risk indicators. The treatment coping style, psychological resilience, quality of life and sleep quality of the two groups were compared.Results:After intervention, the face dimension score of the observation group was higher than that of the control group, and the avoidance and yield dimension scores were lower than those of the control group, and the differences were statistically significant ( P<0.05). After intervention, the scores of resilience, strength and optimism of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05). After intervention, the scores of interpersonal tension, depression, anxiety and fear of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05). After intervention, the total score of sleep quality and scores of all dimensions of the observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Multidimensional intervention strategies based on sensitive risk indicators can improve the treatment enthusiasm and psychological resilience of patients with uterine fibroids complicated with climacteric syndrome, reduce their negative emotion and improve their sleep quality.

Objective:To explore the role of tutorial system combined with TBL teaching method in standardized residency training of the department of rheumatology and immunology.Methods:Sixty residents who participated in standardized training in the department of rheumatology and immunology of our hospital from July 2017 to July 2018 were divided into experimental and control groups according to the period of training. The experimental group adopted the tutorial responsibility system and TBL teaching method, and the control group adopted the traditional residency training mode. The clinical and scientific research abilities of the two groups were compared, and the questionnaires of satisfaction were compared. The statistical analysis was carried out by SPSS 19.0 software.Results:The examination results, scientific research ability and questionnaire survey satisfaction of the tutorial responsibility system combined with TBL teaching method group were higher than those of the traditional teaching group, with statistical significance ( P<0.05 or P<0.01). Conclusion:The tutorial responsibility system combined with TBL teaching method can effectively improve the diagnosis and treatment thinking ability, practical operation skills, clinical scientific research ability, self-study ability and team consciousness, and provide new ideas and methods for improving the quality of standardized residency training.

Objective:To explore the clinical teaching effect of case-based learning combined with diagnosis and treatment guidelines in standardized residency training in the department of rheumatology and immunology.Methods:Forty standardized trainees were randomized into two groups. One was the observation group, which adopted case-based learning combined with diagnosis and treatment guidelines. The other one was the control group, which performed the traditional clinical teaching mode. After 4 weeks, the assessment and satisfaction evaluation were carried out among the two groups. SPSS 19.0 was used for t test and Mann-Whitney test. Results:Students in observation group showed significantly better ability of physical examination and case analysis than those in the control group. The satisfaction degree of the students in the observation group was significantly higher in terms of diagnosis and treatment standard, clinical thinking, problem solving ability, self-learning ability and personal profession benefits than that in the control group.Conclusion:Case-based learning with diagnosis and treatment guidelines is an ideal teaching method combining theory with practice perfectly, which can significantly improve the effect of clinical teaching of standardized residency training in the department of rheumatology and immunology.

Objective To explore the effects of ring finger protein 43 (RNF43) on fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).Methods Synovial tissues from patients with RA treated by knee arthroplasty were used to isolate FLSs by type 2 collagenase.RNF43 lentivirus overexpressing plasmid was constructed and transfected in to RA-FLS.After successful transfection,RNA and super natant of RA-FLS were extracted.QRT-polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)-1,MMP-3 and MMP-13.Data were analyzed with Student's t test.Results Transfection efficiency could meet the test requirements when the multiplicity of infection was 40 and was in conjunction with appropriate concentration of polybrene.The mRNA of RNF43 increased for 26158-fold than the control group.In vitro,compared with the control group,RNF43 could significantly inhibit the mRNA of MMP-1,MMP-3 and MMP-13 and MMP-13 [(0.19±0.06),t=28.314,P＜0.05;(0.28±0.07),t=23.413,P＜0.05;(0.21±0.09),t=18.365,P＜0.05]and the protein of MMP-1,MMP-3 and MMP-13 and MMP-13 [(31.0±9.4) pg/ml,(17.1±2.1) pg/ml,t=3.198,P=0.029],MMP-3 [(38.7±8.1) pg/ml,(24.9±3.5) pg/ml,t=3.514,P=0.015],MMP-13 [(35.9±5.4) pg/ml,(20.6±2.9) pg/ml,t=5.632,P=0.001].Conclusion The results of study suggest that RNF43 could inhibit the secretion of MMPs in RA-FLS by suppressing the activity of Wnt signal pathway.

OBJECTIVE:To establish a method for the rapid identification of Xiangsha pingwei pill(watered pill)from different manufacturers. METHODS:Near-infared spectroscopic method was conducted to collect the infrared spectroscopy of 95 batches of Xiangsha pingwei pill(watered pill) from 5 manufacturers,first derivative was combined with vector normalization to analyze the spectral data,mathematical models were established and validated. RESULTS:When the CI value was 5.6,the established model can identify samples from Li Shizhen Pharmaceutical Group Co.,Ltd. quickly,the model was validated to be achievable;and when the CI value was 4.7,the established model can identify Samples from Jinma Pharmaceutical Co.,Ltd. in Shangqiu city quickly, the model was validated to be achievable. CONCLUSIONS:The method is convenient,rapid and non-destructive,and can identify different Xiangsha pingwei pill(watered pill)from different manufacturers quickly.

Objective To optimize the culture method for rheumatoid arthritis fibroblast-like synoviocytes in vitro,and observe the effect of Dishevelled (Dvl) 2 on vascular endothelial growth factor (VEGF) in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS).Methods Synovium from RA patients who underwent knee arthroplasties were cut into small piece,and RA-FLS were isolated and cultured in vitro using tissue block method.Dvl 2 lentivirus overexpressing plasmid was constructed and transfected into RAFLS.Q-polymerase chain reaction (PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA and protein expression levels of VEGF.Then we used 10 ng/ml tumor necrosis factor (TNF)-α recombinant protein to stimulate the transfected RA-FLS.24 h after stimulation,mRNA and protein expression of VEGF were detected again.Student's t test was used for two group analyses.Results RA-FLS was successfully isolated and cultured in vitro.The multiplicity of infection was 30 and was in conjunction with appropriate concentration of polybrene to promote transfection.Transfection efficiency could meet the test requirements.The mRNA of Dvl 2 increased for 79-fold than the control group.Compared with the control group,Dvl 2 could mildly inhibit RA-FLS secretion of VEGF.After TNF-α stimulation,Dvl 2 could significantly inhibit the VEGF's mRNA (2.15±0.10,2.92±0.47 fold,t=-3.924,P=0.003) and protein [(285±100) pg/ml,(155±61) pg/ml,t=-2.714,P=0.022] expression compared with the control group.Conclusion Dvl 2 can inhibit the effect of TNF-α induced secretion of VEGF in RA-FLS.The specific mechanism needs further study.

Objective To evaluate the dosage regimen of sulfasalzine combined with recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR) in the induction and maintenance of remission in active ankylosing spondylitis.Methods This study enrolled 100 ankylosing spondylitis patients with disease duration for less than five years who were treated with sulfasalzine and rhTNFR combination therapy.Patients were randomly assigned to three groups six weeks later:patients in the G1 group received sulfasalzine combined with rhTNFR at a 25 mg dosage twice each week.Patients shifted to monotherapy with sulfasalzine six weeks later:patients in G2 group received sulfasalzine combined with rhTNFR at 25 mg dosage per week.Patients were switched to monotherapy of sulfasalzine twelve weeks later:patients in G3 group received sulfasalzine combined with rhTNFR at 25 mg dosage once every ten days.Patients were changed to monotherapy of sulfasalzine seventeen weeks later.The whole treatment lasted for 24 weeks.All participants were followed up at week 0,6,12,18,24 respectively and were evaluated by BASDAI 50.The primary end-point of this study was the percentage of patients achieved BASDAI 50 remission.Data were analyzed with SPSS version 17.0.Independent t-test and x2 test were adopted to analyze data.Results 90％ of patients treated with combination therapy reached BASDAI50 at the 6th week.All patients in the G1 group achieved BASDAI 50 remission at 12th week,but the percentage dropped to 68.7％ at 18th week,which gradually decreased to 37.5％ at the 24th week.In G2 group,93.9％ patients reached BASDAI50,which declined to 81.8％ at the 18th week.The whole number accounted for 60％ at the end point of 24th week.In G3 group,85.7％ patients achieved BASDAI50 at the 12th week,accounted for 74.3％ at 18th week,and declined to 68.6％ at the 24th week.G3 group of patients presented a significantly higher rate than other groups(P＜0.05).Conclusion Sulfasalzine and rhTNFR combination therapy can gain remission in active AS patients after treated for six weeks.Doctors may extend TNF antagonist treatment in order to achieve long-term remission.

ObjectiveTo investigate the expression and significance of CD28- cells, CD4+ and CD8+T lymphocytes in the peripheral blood and synovial fluid in patients with rheumatoid arthritis ( RA ). Methods The expression of CD28, CD4+, CD8+ T lymphocytes and inducible co-stimulator(ICOS) in the peripheral blood and synovial fluid in 45 patients with RA were detected by three-color flow cytometry. Independent sample's t test was used for statistical analysis between the two groups. ResultsSynovial fluid CD4+CD28+ICOS+, CD4+CD28- ICOS+ , CD8 + CD28 + , CD8 + CD28 + 1COS+ T lymphocytes were significantly increased than the peripheral blood in RA patients[(36±19)％ vs (15±8)％, t=-4.234, P＜0.01; (2.1±2.2)％ vs (0.6±1.4)％, t=-3.143, P＜0.01; (62±15)％ vs (47±18)％, t=-2.885, P＜0.01; (9±9)％ vs (3±3)％,t=-2.131, P＜0.05], Synovial fluid CD8+CD28-T lymphoc-ytes were significantly reduced than the peripheral blood[(38±15)％ vs (54±18)％, t=2.975, P＜0.01], Synovial fluid CD8+ CD28-ICOS+, CD4+CD28+and CD4+ CD28- T lymphocytes had no significant difference than the peripheral blood (P＞0.05). Compared with peripheral blood in the same patients with RA, CD4+CD28+ ICOS+, CD8+ CD28+ T lymphocyteswere significantly increased[(38±18)％ vs (16±10)％, t=-4.065, P＜0.01 ; (61±16)％ vs (41±21)％, t=-4.065,P＜0.01], CD8+CD28-T was significantly reduced[(39±16)％ vs (59±21)％, t=2.949, P＜0.01]. The level of CD4+ CD28-, CD8+ CD28-, CD28-ICOS+ T lymphocytes in the active and remission patients with RA was not significantly different (P＞0.05). ConclusionSynovial fluid CD28T lymphocyte subsets disturbance and the abnormal expression of ICOS in patients with RA may play important roles in the mechanism of joint damage.