OBJECTIVE: It has been reported that the mRNA expression of serine protease 23 (PRSS23) was increased in skin fibroblasts from systemic sclerosis patients (SSc). The purpose of this study is to explore the pathogenetic effect and mechanism of PRSS23 in skin fibrosis of SSc. METHODS: The expression of PRSS23 in skin tissues from the SSc patients and healthy controls was detected by immunohisto-chemistry. Fibroblasts isolated from fresh skin tissue were used to detect the expression of PRSS23 by real-time quantitative PCR (RT-qPCR) and Western blot. Overexprssion of PRSS23 in BJ, the fibroblasts cell line of skin, was constructed by lentivirus. After stimulation with 400 μmol/L hydrogen peroxide for 12 h, Annexin V/7-AAD staining was used to detect apoptosis of fibroblasts; flow cytometry and Western blot were used to detect the expression of apoptosis-related protein cleaved Caspase-3. The expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fibroblasts was detected by RT-qPCR and enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the healthy controls, the expression of PRSS23 in skin tissues of the SSc patients was significantly increased [4.952 (3.806-5.439) vs. 0.806 (0.395-1.173), P < 0.001], and fibroblast was the main cell that expressed PRSS23. The mRNA [27.59 (25.02-30.00) vs. 1.00, P < 0.001] and protein [0.675 (0.587-0.837) vs. 0.451 (0.342-0.502), P=0.029] of PRSS23 in skin fibroblasts isolated from the SSc patients were significantly up-regulated. Compared with the control group, the anti-apoptotic ability of skin fibroblasts overexpressing PRSS23 was enhanced, and the proportion of apoptotic cells was significantly reduced after hydrogen peroxide induction [(5.043±1.097)% vs. (17.480±3.212)%, P=0.022], the expression of apoptosis-related protein cleaved Caspase-3 was also markedly reduced [(0.718±0.022) vs. (1.422±0.105), P=0.003]. In addition, the mRNA [(99.780±1.796) vs. (1.000±0.004), P < 0.001] and protein [(211.600±2.431) ng/L vs. (65.930±1.768) ng/L, P < 0.001] of IL-6 in the fibroblasts overexpressing PRSS23 were significantly up-regulated; the mRNA[(3.555±0.555) vs. (1.000±0.004), P < 0.001] and protein levels [(41.190±0.949) ng/L vs. (31.150±0.360) ng/L, P < 0.001] of TNF-α in the fibroblasts overexpressing PRSS23 were also significantly up-regulated. CONCLUSION The expression of PRSS23 is increased in skin fibroblasts of SSc patients. PRSS23 can inhibit cell apoptosis, promote the secretion of inflammatory factors such as IL-6 and TNF-α, and regulate the process that skin fibroblasts transform into pro-inflammatory type. So, PRSS23 is associated with the development of skin fibrosis.
Humans ; Scleroderma, Systemic/enzymology* ; Fibroblasts/pathology* ; Apoptosis ; Skin/metabolism* ; Fibrosis ; Interleukin-6/metabolism* ; Caspase 3/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Male ; Female ; Cells, Cultured ; RNA, Messenger/metabolism* ; Middle Aged ; Adult ; Serine Endopeptidases/genetics*

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objective:To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline.Methods:This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index.Results:The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] ( Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions:Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.

Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27％.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.