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Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocyte function due to defective NADPH oxidase (phox). Compared with the common types of CYBB/gp91phox, NCF1/p47phox, and CYBA/p22phox deficiency, NCF4/p40phox deficiency is a mild and atypical form of CGD without invasive bacterial or fungal infections. It can be diagnosed using serum-opsonized E.coli as a stimulus in dihydrorhodamine (DHR) assay. Patients with CYBC1/Eros deficiency, a new and rare form of CGD, present as loss of respiratory burst and gp91phox expression in phagocytes. Neutrophils from patients with CGD are deficient in neutrophil extracellular traps (NETosis), autophagy, and apoptosis. The hyper-activation of NF-ĸB and inflammasome in CGD phagocytes also lead to long-lasting production of pro-inflammatory cytokines and inflammatory manifestations, such as granuloma formation and inflammatory bowel disease-like colitis. Patients with CGD and X-linked female carriers also have a higher incidence of autoimmune diseases. The implementation of antimicrobial, anti-fungal, and interferon-γ prophylaxis has greatly improved overall survival. Residual NADPH oxidase activity is significantly associated with disease severity and the chance of survival of the patient. New therapeutic approaches using immunomodulators for CGD-related inflammatory manifestations are under investigation, including pioglitazone, tamoxifen, and rapamycin. Hematopoietic stem cell transplantation (HSCT) is the curative treatment. Outcomes of HSCT have improved substantially over the last decade with overall survival more than 84–90%, but there are debates about designing optimal conditioning protocols using myeloablative or reduced-intensity regimens. The gene therapy for X-linked CGD using hematopoietic stem and progenitor cells transduced ex vivo by lentiviral vector encoding the human gp91phox gene demonstrated persistence of adequate oxidase-positive neutrophils in a small number of patients. Gene therapy using genome-editing technology such as CRISPR/Cas9 nucleases is a promising approach for patients with CGD in the future.

The Chang Gung Research Database (CGRD) is a de-identified database derived from original medical records of Chang Gung Memorial Hospital (CGMH), which comprises seven medical institutes located from the northeast to southern regions of Taiwan. The volume of medical services performed in CGMH is large, and clinical and scientific studies based on the CGRD are reported to be of high quality. However, the CGRD as a useful database for research has not been analyzed before. The objective of the study was to analyze the CGRD with regard to its characteristics and coverage of Taiwan's population. We performed a nationwide cohort study using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). All patients who had any medical record of outpatient visits or admission between January 1, 1997, and December 31, 2010, were included, and the sex ratio, age distribution, socioeconomic status, urbanicity, severity of illness, prevalence of specific disease, and coverage of the CGRD were analyzed. The sex ratio, age distribution, socioeconomic status, and urbanicity of the population of the CGRD are different from those of Taiwan NHIRD and medical centers in Taiwan (all the pairwise p < 0.05). The severity of comorbidities, and prevalence of specific diseases of the population of the CGRD are significantly higher than those of Taiwan NHIRD and medical centers in Taiwan for both outpatient and inpatient samples (all the pairwise p < 0.05). The overall coverage of the CGRD was 21.2% for outpatients and 12.4% for inpatients. The disease-specific coverage of the CGRD was 27-34% for outpatients and 14-21% for inpatients. The CGRD is a multi-institutional, original medical record-based research database with high overall and disease-specific coverage of Taiwan. The population of the CGRD has significantly higher severity of comorbidities, and prevalence of specific diseases than those of Taiwan NHIRD and medical centers in Taiwan.

Background The pathogenesis of lupus nephritis (LN) remains not fully understood. In this study, we aimed to explore the pathogenic roles of autoantibodies against human renal glomerular endothelial cells (HRGEC) in LN patients. Methods The serum levels of anti-HRGEC antibodies in systemic lupus erythematosus (SLE) patients without LN and LN patients were determined by cell-based enzyme-linked immunosorbent assay (ELISA). Monoclonal IgG anti-HRGEC antibodies were subsequently generated from LN patients. The binding activities of these monoclonal antibodies to HRGEC, their cross-reactivity with double-stranded DNA (dsDNA), and the ability to activate HRGEC were further evaluated. Results LN patients had higher serum levels of IgG anti-HRGEC antibodies than SLE patients without LN and healthy controls. Four monoclonal IgG anti-HRGEC antibodies (LN1–4) were obtained; LN1 and LN2 were IgG3 while LN3 and LN4 were IgG1. Among these monoclonal antibodies, LN1–3 were cross-reactive with dsDNA. The functional assays showed that compared with IgG1/IgG3 isotype controls, LN3 had an effect on HRGEC to enhance interleukin (IL)-6 production, LN4 could enhance IL-8 and monocyte chemoattractant protein (MCP)-1 production, and LN1–3 possessed the ability to induce interferon (IFN)-α production by HRGEC. Moreover, the removal of DNA on the HRGEC surface by DNAse 1 did not interpose the binding of LN1–3 to HRGEC and the effects of LN1–3 on IFN-α induction by HRGEC. Conclusions Some IgG anti-HRGEC antibodies in LN patients had the ability to enhance endothelial proinflammatory cytokine (IL-6, IL-8, and MCP-1) production, and some could induce the DNA-independent production of IFN-α by HRGEC.

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate in vivo protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). In vitro , human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The in vivo effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

In addition to IgA, the deposition of complement (C)3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP). The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP. Plasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA). The expression of C3a receptor (C3aR), C5a receptor (CD88), E-selectin, intercellular adhesion molecule 1 (ICAM-1), C3, C5, interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d) was evaluated either by flow cytometry or by ELISA. At the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001), C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001), and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 μg/ml, p < 0.0001), but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner. In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels.

Behçet’s disease (BD) is a chronic, vasculitic disorder affecting all sizes of vessels. The disease rarely onsets at childhood and an early diagnosis is often challenging. Oral ulceration and fever of unknown cause are common initial manifestations that might confuse other inflammatory disorders. The clinical manifestation pattern in pediatric BD is heterogeneous and varies in different genders, ethnicities, and geographic regions. There are also some differences in clinical presentations and prognosis between pediatric and adult BD. The disease also affects children at an extremely young age with mostly benign outcomes compared with that in older children. A limited number of studies reported issues about pediatric BD, let alone studies of children’s treatments. Currently, the recommendation of the treatment in pediatric BD is according to the guideline of adult BD. The heterogeneity of clinical features makes the treatment more complicated. The main goal of the treatment is to control the inflammatory process and prevent recurrences. We will discourse the definition, epidemiology, clinical features, diagnosis, and treatment of pediatric BD in this review.

Palpable purpura, gastrointestinal symptoms, joint involvement, and renal disease characterize immunoglobulin A vasculitis (IgAV). Renal involvement ranging from mild proteinuria to severe nephritic or nephrotic syndrome highlights the importance of monitoring kidney function in patients with IgAV. Recognizing these key features is crucial for early diagnosis and appropriate management to prevent long‐term complications related to kidney disease. However, the pathogenesis of IgAV remains unclear. Disease mechanisms involve various factors, including the interplay of aberrantly glycosylated IgA, anti‐endothelial cell antibodies, and neutrophils following infection triggers, which are the main pathogenic mechanisms of IgAV. Insights from cases of IgAV related to Coronavirus disease 2019 have offered additional understanding of the connection between infection and IgAV pathogenesis. This review provides a valuable resource for healthcare professionals and rheumatology researchers seeking a better understanding of the clinical features and pathophysiology of IgAV.

Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with various cancers. However, it remains unclear whether ARBs confer a survival benefit on patients with oral squamous cell carcinoma (OSCC). Here, we assessed the associations between ARB use and survival in patients with OSCC of different stages. This was a 10-year retrospective cohort study of OSCC patients. We enrolled 7,558 patients diagnosed with oral cancer between January 2007 and December 2017 whose details had been entered into the Chang Gung Research Database. Seven hundred and fourteen patients were recruited from the Chang Gung Research Database after performing 1:1 propensity score-matching between ARB users and non-users. Cox's regression models with adjusted covariates were employed to detect factors influencing the survival rates of patients with OSCC. Kaplan-Meier analysis revealed that the overall survival (OS) rate of 180-day ARB users increased (p = 0.038). Cox's regression models indicated that ARB use, younger patients, early-stage OSCC, and patients without diabetes mellitus were independently prognostic of improved OS. Increased OS was more prominent in 180-day ARB users in stage III, Iva, and IVb categories. ARB use for more than 180 days is associated with an increased survival rate and is a positive, independent prognostic factor in patients with OSCC. A further two-arm study should be conducted to confirm the clinical usefulness of ARBs in OSCC patients.

Juvenile Idiopathic Arthritis (JIA) is the most common chronic arthritis in children, causing significant joint inflammation and complications. This study evaluates the incidence, prevalence, and treatment patterns of JIA in Taiwan, focusing on biologic therapy. A retrospective observational study utilized data from the National Health Insurance Research Database (NHIRD) for the period 2011-2020. Patients diagnosed with JIA were identified, and the annual incidence and prevalence rates were calculated. Treatment patterns, particularly regarding biologics, were assessed. Subgroup analysis compared patients diagnosed with spondyloarthritis (SpA) versus non-SpA within the JIA cohort. Two thousand and thirty-three JIA patients were included. The annual prevalence ranged from 18.0 to 24.2 per 100,000 populations under 16 years old, with an incidence of 5.22 to 6.57 per 100,000. A male predominance was noted (male-to-female ratio: 1.08-1.52:1). The JIA-SpA subgroup comprised 49.2% of the JIA cohort. Compared to Non-SpA patients, the JIA-SpA subgroup showed male predominance (70.7% vs. 44.4%, p<0.0001), later age of onset, and lower biologic use (15.2% vs. 23.1%, p<0.001). Tumor necrosis factor alpha inhibitors were the most used biologics, with a continuation rate of 49.1%. Switching occurred in 13.2% of patients, mostly without interruption within a treatment gap of 60 days. Discontinuation without subsequent biologic therapy was observed in 9.5% of patients, while 28.2% restarted therapy after a treatment interruption of more than 60 days. This study highlights the epidemiological characteristics and treatment patterns for JIA in Taiwan, focusing on biologic therapies. Most patients maintained consistent biologics, with a small proportion able to discontinue them, emphasizing the need for region-specific management strategies.

Some studies have indicated that the use of prokinetic agents may reduce pneumonia risk in some populations. Nasogastric tube insertion is known to increase the risk of pneumonia because it disrupts lower esophageal sphincter function. The aim of this study was to evaluate whether prokinetic agents could protect long-term nasogastric tube-dependent patients in Taiwan from being hospitalized for pneumonia. A case-crossover study design was applied in this study. Long-term nasogastric tube-dependent patients who had a first-time admission to a hospital due to pneumonia from 1996 to 2013 that was recorded in the Taiwan National Health Insurance Research Database were included. The case period was set to be 30 days before admission, and two control periods were selected for analysis. Prokinetic agent use during those three periods was then assessed for the included patients. Conditional logistic regression was used to calculate the odds ratio (OR) for pneumonia admission with the use of prokinetic agents. A total of 639 first-time hospitalizations for pneumonia among patients with long-term nasogastric tube dependence were included. After adjusting the confounding factors for pneumonia, no negative association between prokinetic agent use and pneumonia hospitalization was found, and the adjusted OR was 1.342 (95% CI 0.967-1.86). In subgroup analysis, the adjusted ORs were 1.401 (0.982-1.997), 1.256 (0.87-1.814), 0.937 (0.607-1.447) and 2.222 (1.196-4.129) for elderly, stroke, diabetic and parkinsonism patients, respectively. Prokinetic agent use had no negative association with pneumonia admission among long-term nasogastric tube-dependent patients in Taiwan.