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Granulomatous polyangiitis (GPA) is a rare autoimmune disease that can involve multiple systems throughout the body, including the ear, nose, upper and lower respiratory tracts. It is classified as an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Telitacicept is a novel recombinant fusion protein targeting B-lymphocyte stimulator (BLyS). Telitacicept can inhibit the development and maturation of abnormal B cells by blocking BLyS, and inhibit the production of antibodies by abnormal plasma cells by blocking APRIL (A proliferation-inducing ligand), which is expected to become a new drug for the treatment of GPA. We report a 64-year-old man diagnosed at our hospital with GPA involving multiple systems including kidneys, lungs, nose and ears. Renal involvement was severe, with a clinical characteristic of rapidly progressive glomerulonephritis and a pathologic manifestation of crescentic nephritis with plasma cell infiltration. The patient was treated with hormones, immunoglobulins and cyclophosphamide (CYC) with the addition of telitacicept and a rapid reduction in hormone dosage. The patient's renal function improved significantly within a short period of time, and his hearing and lung lesions improved significantly. At the same time, he did not develop serious infections and other related complications. Our report suggests that short-term control of the patient's conditions is necessary in GPA patients with organ-threatening disease. Telitacicept combined with CYC and glucocorticoids may be an induction therapy with safety and feasibility. However, more clinical trials are needed to validate the efficacy and safety of the therapeutic regimen.

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With the overwhelmingly booming trend of innovation in medical devices, more and more innovative products are in urgent need of classification before marketing. Medical device classification is not only a basis of regulation but also a key factor affecting industry innovation and development. In view of the current situation of classification process in China has been time-consuming, this study discusses an E-classification framework including its classification basis, method, dimensions and technical roadmap, etc. based on medical devices regulations in China illustrated by the classification of radio therapeutic equipment, taking advantage of digitalization, networking and intelligence, and explores the improvement of classification efficiency to promote the innovation and development of medical devices.

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Objectives: Heparan sulfate (HS) forms heparan sulfate proteoglycans (HSPGs), such as syndecans (SDCs) and glypicans (GPCs), to perform biological processes in the mammals. This study aimed to explore the role of HS in dilated cardiomyopathy (DCM). Methods: Two high throughput RNA sequencing, two microarrays, and one single-cell RNA sequencing dataset of DCM hearts were downloaded from the Gene Expression Omnibus (GEO) database and integrated for bioinformatics analyses. Differential analysis, pathway enrichment, immunocytes infiltration, subtype identification, and single-cell RNA sequencing analysis were used in this study. Results: The expression level of most HSPGs was significantly upregulated in DCM and was closely associated with immune activation, cardiac fibrosis, and heart failure. Syndecan2 (SDC2) was highly associated with collagen I and collagen III in cardiac fibroblasts of DCM hearts. HS biosynthetic pathway was activated, while the only enzyme to hydrolyze HS was downregulated. Based on the expression of HSPGs, patients with DCM were classified into three molecular subtypes, i.e., C1, C2, and C3. Cardiac fibrosis and heart failure were more severe in the C1 subtype. Conclusion: Heparan sulfate is closely associated with immune activation, cardiac fibrosis, and heart failure in DCM. A novel molecular classification of patients with DCM is established based on HSPGs.

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Patients with aortic stenosis and low left ventricular ejection fraction (LVEF) would benefit from transcatheter aortic valve replacement. However, the safety and efficacy of transcatheter aortic valve replacement in patients with aortic regurgitation and left ventricular dysfunction remains unknown.We defined LVEF < 50% as left ventricular dysfunction. A total of 27 symptomatic patients with aortic regurgitation and ejection fraction < 50% underwent transcatheter aortic valve replacement using the J-Valve™ system (JieCheng Medical Technology Co, Ltd, Suzhou, China) in Zhongshan Hospital, Fudan University, from May 2014 to June 2019. Procedural and postoperative clinical outcomes were analyzed according to Valve Academic Research Consortium-2 (VARC-2) criteria.All patients (eight females; 70.6 ± 7.1 years) were considered to be at least intermediate surgical risk and/or severe comorbidity precluding for surgical aortic valve replacement (logistic European System for Cardiac Operative Risk Evaluation, 16.8 ± 9.5%, range 4.6% to 37.9%) by a multidisciplinary heart team. Transapical implantations were successful in 26 (96.3%) patients. All-cause mortality was 3.7% in the latest follow-up (25-590 days, median 369 days). Significant improvements in LVEF, left ventricular end-diastolic, and systolic dimensions were observed after procedure (from 40.3 ± 6.7% to 50.8 ± 10.5%, P < 0.001; from 65.1 ± 8.9 mm to 56.0 ± 9.6 mm, P = 0.002; from 52.2 ± 9.8 mm to 35.9 ± 13.4 mm, P < 0.001, respectively). No patient had aortic stenosis and paravalvular leak more than moderate and heart function improvement was obtained in the majority of patients at 1-year follow-up.Transcatheter aortic valve replacement using the J-Valve™ system is a reasonable alternative for patients with aortic regurgitation and left ventricular dysfunction regarding promising short-term outcomes.

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Punicalagin, a major ellagitannin isolated from pomegranate, is proved to have various pharmacological activities with an undefined therapy mechanism. The objective of this research was to demonstrate the effect of punicalagin on anti-inflammatory and angiogenic activation in human umbilical vein endothelial cells (HUVECs) and their potential mechanisms. Endothelial-leukocyte adhesion assay was applied to evaluate primary cultures of HUVECs activation following tumor necrosis factor alpha (TNF-α) treatment. The endothelial cell proliferation, migration, permeability and tube formation were assessed by EdU assay, wound migration assay, trans-endothelial electrical resistances (TEER) assay, and capillary-like tube formation assay, respectively. In addition, the expression of relevant proteins was assessed using Western blot analysis. We confirmed that punicalagin could reduce the adhesion of human monocyte cells to HUVECs in vitro and in vivo. Further, punicalagin decreased the expression of mRNA and proteins of ICAM-1 and VCAM-1 in HUVECs. Moreover, punicalagin inhibited permeability, proliferation, migration, and tube formation in VEGF-induced HUVECs, suppressed IKK-mediated activation of NF-κB signaling in TNF-α-induced endothelial cells, and inhibited vascular endothelial growth factor receptor 2 (VEGFR2) activation and downstream p-PAK1. Our findings indicated that punicalagin might have a protective effect on HUVECs activation, which suggested that punicalagin functions through an endothelial mediated mechanism for treating various disorders such as, cancer, rheumatoid arthritis, and cardiovascular disease.

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BACKGROUND: Transcatheter mitral valve-in-valve (TMVIV) procedure with aortic transcatheter heart valves has recently become a less invasive alternative for patients with mitral bioprosthetic dysfunction. This study reports the initial experience of TMVIV implantation using the J-Valve System (JieCheng Medical Technology Corporation Ltd., Suzhou, China). METHODS: A retrospective observational multicenter study was conducted to evaluate the short-term outcomes of TMVIV. In total, 26 consecutive patients with symptomatic bioprosthetic failure at eight hospitals underwent TMVIV using the J-Valve System between May 2019 and June 2021. Procedural results and clinical outcomes were analyzed using the Mitral Valve Academic Research Consortium criteria. RESULTS: The mean age was 75.3 ± 7.1 years and 69.2% of patients were female. The mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 12.3 ± 8.3%. The technical success rate was 96.2%. Nine of the 26 patients (34.6%) were implanted with a J-Valve of a size equal to the internal diameters of the deteriorated prostheses. At the 30-day and 1-year follow-ups, all-cause mortality was 3.8 and 16.0% and the stroke rates were 0 and 12.0%, respectively. Device-related mortality was 0% and the mean mitral valve gradient was 6.4 ± 2.7 mm Hg. No patient experienced device embolization, left ventricular outflow tract obstruction, or mitral valve reintervention. Postprocedural mitral regurgitation was none or trace in all the patients. All the patients were in the New York Heart Association (NYHA) class ≤ II at the last follow-up. CONCLUSION: Transcatheter implantation of the J-Valve System in high-risk patients with mitral bioprosthetic dysfunction was found to be a reasonable alternative and associated with good short-term outcomes.

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To explore the potential relationship between dairy product consumption and bladder cancer risk, we retrieved eligible studies published up to March 15, 2018, via online database search and manual review of the selected articles. Summary relative risk (RR) estimates were calculated using random-effects models based on high to low intake values. Inter-study heterogeneity was explored using stratified analyses of study design, geographic region, or whether studies adjusted for the confounders age, sex, body mass index, smoking, and education level. We extracted data from 16 studies on milk (5,193 subjects) and 10 studies on dairy products (20,434 subjects). The total study population included 220,952 individuals. Dairy product intake and bladder cancer risk were significantly associated, and milk intake and bladder cancer risk more so. Stratified analysis revealed that the trend was more pronounced in case-control studies, and in studies with impact factor <3 and in Asia. The relationship was confirmed after adjusting for sex and Newcastle-Ottawa Scale score of 7 and 8. Our study shows an inverse association between milk consumption and bladder cancer risk.

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BACKGROUND & OBJECTIVE: X-ray radiography is the first choice for detecting chest diseases. However, "visual obstacles" caused by the overlaps between ribs and lung in chest radiography affects the observation and analysis of chest diseases. The objective of this study was to investigate the value of direct digital radiography (DR) dual-energy technique in diagnosis of chest disease located in the overlaps between ribs and lung. METHODS: Thirty-five cases of chest tubercular diseases located in the overlaps between ribs and lung were examined using direct digital radiography (DR) dual-energy technique. RESULTS: Ratings of dual-energy technique radiography in detecting chest tubercular diseases were 94.3% whereas the ratings of DR radiography were 45.7%. Bone and soft tissue can be separated in the radiography using dual-energy technique. CONCLUSION: DR dual-energy technique not only increases the visibility towards chest tubercular disease, but also discriminates the location (ribs or lung) of chest tubercular disease.

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