Objective To study the effects of chimeric B7 antibodies on mononuclear cells from patients with ankylosing spondylitis (AS).Methods Chimeric antibodies of ch4E5 and chlD1 against B7 with a final concentration of 5 μg/ml were respectively added into culture media of mononuclear cells from patients with AS.Two other groups including huIgG-treated and untreated culture medium of mononuclear cells from patients with AS were set up as the controls.The culture medium of mononuclear cells from healthy subjects were prepared as normal control group.The disparities of mononuclear cell death in culture among each group were analyzed by using micro-lymphocyte cytotoxicity test (MLCT).The expression of membrane molecules were analyzed by FCM.The concentrations of cytokines in culture media were measured by ELISA.Results Both groups treated with the chimeric antibody showed lower scores for cell death than untreated group as indicated by MLCT (P＜0.01).FCM analysis demonstrated that both CD4/CD8 ratio (P ＜0.05) and membrane expression of CD154 (P＜0.01) decreased in chimeric antibody treated groups,but the number of CD4+CD25high Treg cells (P＜0.01) increased as compared with those in untreated group.The concentrations of IL-2 and TNF-α were down-regulated (P＜0.05) in chimeric antibody treated groups,while IL-4 and TGF-β were up-regulated (P＜0.02) as compared with those in untreated group.Conclusion Chimeric B7 antibodies might affect the expression of T cell membrane molecules and the cytokine production by mononuclear cells through B7/CD28 and CD4O/CD154 signaling pathways in patients with AS.

Objective:To observe heart rate circadian rhythm in patients with chronic kidney disease (CKD) stage 5 and to analyze the effects of parathyroidectomy (PTX) on heart rate circadian rhythm in severe secondary hyperparathyroidism (SHPT) patients.Methods:A cross-sectional observation was performed in 213 patients with CKD stage 5 and 96 controls, and the patients were divided into those with severe SHPT (PTX group, n=70) and without severe SHPT (non-PTX group, n=143). Forty-six PTX patients were followed up prospectively. The baseline data were compared among these groups. Holter electrocardiogram was performed for each participant. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Multiple linear regression analysis was used to analyze the related factors of heart rate circadian rhythm in patients with CKD stage 5. Results:The 24-hour, daytime and nighttime mean heart rate in patients with CKD stage 5 were all higher than those in controls, especially in PTX group (all P<0.05). The night/day heart rate ratios of controls and CKD stage 5 patients were (0.81±0.08) and (0.91±0.08) respectively ( P<0.01). Correlation analysis showed 24-hour and daytime or nighttime mean heart rate in patients with CKD stage 5 were positively correlated with serum levels of phosphorus and ln(alkaline phosphatase), while nighttime mean heart rate and night/day heart rate ratio were positively related with serum intact parathyroid hormone level. After adjusting with postoperative follow-up period (median time: 10.9 months), 24-hour and nighttime mean heart rate, and night/day heart rate ratio in PTX patients all decreased significantly (all P<0.01). Conclusions:Heart rate is increased and circadian rhythm is abnormal in patients with CKD stage 5, which are related with mineral and bone disorder. PTX significantly decreases 24-hour and nighttime mean heart rate in severe SHPT patients, and improves the heart rate circadian rhythm.

Objective:To investigate the predictive value of abnormal heart rate circadian rhythm for all-cause mortality in stage 5 chronic kidney disease (CKD 5) patients.Methods:The retrospective study was performed in CKD 5 patients enrolled from the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) and the Affiliated BenQ Hospital of Nanjing Medical University from February, 2011 to December, 2019. A total of 159 healthy volunteers were enrolled as the healthy control group during the same period. The circadian rhythm of heart rate was monitored by 24-hour Holter. Related indices (including 24-hour, daytime and nighttime mean heart rate, night/day heart rate ratio, 24-hour maximum heart rate, 24-hour minimum heart rate and difference between maximum and minimum of 24-hour heart rate) were calculated. Non-dipping heart rate was defined as night/day heart rate ratio greater than 0.9. Cox regression model was used to analyze the risk factors of all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve and Log-rank test were used to compare the differences of cumulative mortality between high ratio group (night/day heart rate ratio>0.91) and low ratio group (night/day heart rate ratio≤0.91). The nonlinear relationship between night/day heart rate ratio and all-cause mortality was analyzed by restricted cubic spline plot. Time-dependent receiver operating characteristic (ROC) curve was used to analyze the predictive value of night/day heart rate ratio for all-cause mortality in CKD 5 patients.Results:A total of 159 healthy volunteers and 221 CKD 5 patients were included in this study. There were 123 males (55.66%) and the age was (52.72±13.13) years old in CKD 5 patients. The total median follow-up time was 50.0 months. Compared with controls, 24-hour, nighttime mean heart rate, 24-hour minimum heart rate in CKD 5 patients were increased (all P<0.05), furthermore, the night/day heart rate ratio was higher [(0.91±0.09) vs (0.81±0.08), P<0.001], showing "non-dipping heart rate". However, the 24-hour maximum heart rate and the difference between maximum and minimum of 24-hour heart rate in CKD 5 patients were lower than controls (both P<0.05). Multivariate Cox regression analysis showed that the increased night/day heart rate ratio (per 0.1 increase, HR=1.557, 95% CI 1.073-2.258, P=0.020) was an independent influencing factor for all-cause mortality in CKD 5 patients. Kaplan-Meier survival curve analysis showed that the cumulative mortality of the high ratio group was significantly increased than that of the low ratio group (Log-rank test χ 2=7.232, P=0.007). From the restricted cubic spline plot, there was a linear effect between night/day heart rate ratio and all-cause mortality ( P=0.141), and when night/day heart rate ratio was above 0.91, the risk of all-cause mortality was significantly increased in CKD 5 patients. According to time-dependent ROC curve, the accuracy of night/day heart rate ratio in predicting all-cause mortality was 70.90% even when the survival time was up to 70.0 months. Conclusions:The circadian rhythm of heart rate in CKD 5 patients displays "non-dipping" state. High night/day heart rate ratio is an independent influencing factor for all-cause mortality in CKD 5 patients.

Objective:To investigate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with maintenance hemodialysis (MHD) in Jiangsu province during SARS-CoV-2 pandemic in China from December 7, 2022 to January 27, 2023, and to analyze the influencing factors of all-cause death.Methods:It was a multi-center cross-sectional investigation. Structured questionnaire was used to collect patient information by medical staff of each hemodialysis center (room) as investigators. Part of the demography data and laboratory examination data came from the Jiangsu Province Hemodialysis Data Information System. MHD patients from hemodialysis centers (rooms) at all levels of medical institutions and independent hemodialysis institutions in Jiangsu province during the outbreak of SARS-CoV-2 infection were included, and the clinical characteristics and all-cause mortality of confirmed and suspected cases of SARS-CoV-2 infection were analyzed.Results:Questionnaire surveys and data analysis on 57 278 patients in 407 hemodialysis centers (rooms) were completed, accounting for 90.41% of the total number of MHD patients (63 357 cases) in Jiangsu province during the same period. There were 24 038 cases (41.97%) of SARS-CoV-2 infection and 14 805 cases (25.85%) of suspected infection, which were widely distributed in all dialysis centers in Jiangsu province. After clinical classification of 38 843 confirmed and suspected SARS-CoV-2 infection cases, 3 662 cases were severe and critical cases, accounting for 9.43% of the infected and suspected cases. Among the patients who had completed the questionnaires, there were 1 812 all-cause deaths, with an all-cause mortality rate of 3.16%. Multivariate logistic regression analysis showed that elderly (taking ≤50 years as a reference, 51-59 years: OR=1.583, 95% CI 1.279-1.933, P=0.001; 60-69 years: OR=3.972, 95% CI 3.271-4.858, P<0.001; 70-79 years: OR=7.236, 95% CI 5.917-8.698, P<0.001; ≥80 years: OR=11.738, 95% CI 9.459-14.663, P<0.001), male ( OR=1.371, 95% CI 1.229-1.529, P<0.001), and co-infection with hepatitis B virus (HBV) (positive serum HBV surface antigen, OR=0.629, 95% CI 0.484-0.817, P<0.001) were independent influencing factors for all cause mortality. Receiver-operating characteristic curve analysis showed that the area under the curve for male, age and current HBV infection prediction of all-cause death was 0.529 ( P<0.001), 0.724 ( P<0.001) and 0.514 ( P=0.042), respectively, and the cut-off value for age prediction of all-cause death was 65.5 years old. Compared with patients without HBV infection, MHD patients with HBV infection significantly reduced the proportion of severe and critically ill patients, all-cause hospitalizations and all cause deaths when infected with SARS-CoV-2 (4.99% vs. 6.41%, χ2=6.136, P=0.013; 8.90% vs. 11.44%, χ2=11.662, P<0.001; 2.01% vs. 3.37%, χ2=10.713, P=0.001, respectively). Conclusion:The MHD patients in Jiangsu province are susceptible to SARS-CoV-2. Elderly age and male gender are independent risk factors for death in MHD patients during the epidemic, while the HBV infection may be a protective factor for death of MHD patients infected with SARS-CoV-2.

Objective: This study aimed to reveal the potential clinical and biological functions of frizzled related protein (FRZB) mRNA expression in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods: We used the keyword “lung cancer” to search the data through Gene Expression Omnibus (GEO) database attached to NCBI(National Center of Biotechnology) and download the data of LUAD and LUSC from TCGA (The Cancer Genome Atlas) Database. A total of eight LUAD and six LUSC datasets were incorporated in this analysis. We defined cutoff value of FRZB using Cutoff Finder into the two groups to calculate hazard ratio (HR). Results: We found that high expression level of FRZB mRNA in tumor tissues was a positive prognostic factor for overall survival in LUAD [pooled HR（95%CI）=0.54（0.46-0.64）,P＜0.05 in univariate analysis; pooled HR（95%CI）=0.66（0.54-0.79）,P＜0.05 in multivariate analysis]. Interestingly, there was no similar results in LUSC [pooled HR（95%CI）=1.11（0.67-1.84）,P＞0.05 in univariate analysis; pooled HR（95%CI）=1.13（0.71-1.78）,P＞0.05 in multivariate analysis]. We also found that FRZB may inhibit WNT signal pathway by t-SNE and correlation analysis. By enrichment analysis, FRZB and its most correlated genes were involved in multiple immune-related pathways, such as complement and coagulation cascades, humoral immune response, etc. Conclusion High expression of FRZB mRNA in LUAD was associated with better prognosis of lung adenocarcinoma. These results suggest that FRZB may be used as a potential marker for favorable prognosis of lung adenocarcinoma.

To compare the performance of generalized additive model (GAM) and long short-term memory recurrent neural network (LSTM-RNN) on the prediction of daily admissions of respiratory diseases with comorbid diabetes. Daily data on air pollutants, meteorological factors and hospital admissions for respiratory diseases from Jan 1st, 2014 to Dec 31st, 2019 in Beijing were collected. LSTM-RNN was used to predict the daily admissions of respiratory diseases with comorbid diabetes, and the results were compared with those of GAM. The evaluation indexes were calculated by five-fold cross validation. Compared with the GAM, the prediction errors of LSTM-RNN were significantly lower [root mean squared error (RMSE): 21.21±3.30 vs. 46.13±7.60, <0.01; mean absolute error (MAE): 14.64±1.99 vs. 36.08±6.20, <0.01], and the value was significantly higher (0.79±0.06 vs. 0.57±0.12, <0.01). In gender stratification, RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting female admission (all <0.05), but there were no significant difference in predicting male admission between two models (all >0.05). In seasonal stratification, RMSE and MAE of LSTM-RNN were lower than those of GAM in predicting warm season admission (all <0.05), but there was no significant difference in value (>0.05). There were no significant difference in RMSE, MAE and between the two models in predicting cold season admission (all >0.05). In the stratification of functional areas, the RMSE, MAE and values of LSTM-RNN were better than those of GAM in predicting core area admission (all <0.05). has lower prediction errors and better fitting than the GAM, which can provide scientific basis for precise allocation of medical resources in polluted weather in advance.
Beijing/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Hospitalization ; Humans ; Male ; Memory, Short-Term ; Neural Networks, Computer