Abstract Purpose To report a rare case of biliary candidiasis in a host with normal immunity. Methods Laboratory tests indicated an elevated G level of 1000 pg/ml. Microscopic examination of pathological sections demonstrated multiple, narrow base, budding yeast cells following Grocott's methenamine silver staining and periodic acid‐Schiff staining. Subsequent sequence analysis supported the diagnosis of biliary candidiasis. Results A 31‐year‐old previously healthy man developed obstructive jaundice under no obvious inducement. He experienced cholecystectomy and biliary drainage. Surgical specimens revealed granulomatous chronic inflammation in the gallbladder, liver, bile ducts and mesenteric lymph nodes. He was misdiagnosed with tuberculosis and received antituberculosis treatment. However, his condition did not improve. He was finally diagnosed with biliary candidiasis and administered the antifungal treatment with fluconazole. His symptoms improved after such treatment. Conclusions We reported a case of biliary candidiasis that mimicked IgG4‐RD in a host with normal immunity. Our findings highlighted the need for pathological diagnosis in patients with symptoms resembling IgG4‐RD.
Abstract ObjectivesRemitting seronegative symmetrical synovitis with pitting edema (RS 3 PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS 3 PE.MethodsA total of 51 patients with RS 3 PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy.ResultsA total of forty-eight RS 3 PE patients (94.1%) were available with follow-up data, 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor, and 2 patients were solid tumor. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS 3 PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS 3 PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL] and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS 3 PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS 3 PE.ConclusionsThis study indicated that bFGF was elevated in RS 3 PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS 3 PE.
To the Editor: Systemic lupus erythematosus (SLE) is an autoimmune disease that tends to affect females of childbearing age. There are nearly 4 million people in China currently suffering from SLE, which can cause multiple organ damage in its early stages and seriously affect patients' quality of life.[1,2] Menstrual disorders are common in SLE patients and vary from heavy menstrual bleeding to amenorrhea. The etiology of menstrual irregularities includes the disease activity itself, glucocorticoids (GCs) treatment, and the use of some immunosuppressants.[3] This multicenter, cross-sectional, web-based observational study investigated menstrual irregularity, pregnancy outcomes, and birth outcomes on SLE patients across China. The research was approved by the Ethics Committee of Peking University People's Hospital, China (No. 2019PHB253-01). The patients were informed that consent was implied with completion of the questionnaire, and the process was anonymous and voluntary. A total of 3964 SLE female patients ranging in age between 15 years and 49 years were recruited from 157 hospitals across China [Supplementary Figure 1, https://links.lww.com/CM9/B404]. The patients answered the standardized questionnaire via email or text message under the guidance of a rheumatologist over the phone. Clinical data were collected through questionnaires [Supplementary Materials, https://links.lww.com/CM9/B404], including basic features, menstruation after diagnosis, medications, marriage and fertility status, reproductive history, adverse pregnancy outcomes (APO), and adverse birth outcomes (ABO). The categorized variables were shown as frequency or percentage, and continuous variables were demonstrated as mean ± standard deviation. The Mann–Whitney and chi-squared tests were used to determine any statistical difference between the means and proportions of the two groups. The variables were tested for normality and homogeneity of variance before the Mann–Whitney and chi-squared tests were carried out. Univariate and multivariate logistic regression analyses were used to assess associations between clinical characteristics and menstruation, pregnancy, and neonatal outcomes. A 95% confidence interval (CI) was calculated to identify the independent variable in the binary logistic regression analysis. Differences were considered statistically significant when P < 0.05. Statistical Package for Social Sciences (SPSS 26.0, IBM Corp, Armonk, NY, USA) was used to analyze all data. The mean age of the participants was 30.42 ± 7.40 years. Of these patients, 75.55% experienced menstrual disorders, including light menstrual bleeding (48.99%), shortened menstrual bleeding (23.31%), prolonged menstrual bleeding (13.65%), amenorrhea (10.85%), and heavy menstrual bleeding (7.11%). The proportions of GCs, cyclophosphamide (CYC), and mycophenolate mofetil (MMF) in these patients were 55.17%, 27.22%, and 28.58%, respectively. The percentage of CYC in combination with GC and GC with MMF was 24.09% and 20.51%, respectively. Compared with patients who experienced normal menstruation, patients experiencing abnormal menstruation were older (31.17 ± 7.59 vs. 28.12 ± 6.25 years, P < 0.001), had a higher average body mass index (BMI) (21.69 ± 3.32 vs. 21.32 ± 3.46 kg/m2, P = 0.003), and experienced a longer disease duration (6.28 ± 5.49 vs. 5.38 ± 4.72 year, P < 0.001). The treatment of CYC (37.67% vs. 21.88%, P < 0.001), GCs (75.84% vs. 51.56%, P < 0.001), and MMF (39.67% vs. 21.35%, P < 0.001) were all significantly higher in patients with abnormal menstruation [Supplementary Table 1, https://links.lww.com/CM9/B404]. Binary logistic regression demonstrated that older patients (Odds ratio [OR]: 1.039, 95% CI: 1.016–1.062, P = 0.001), longer disease duration (OR: 1.041, 95% CI: 1.004–1.079, P = 0.029), CYC treatment (OR: 1.830, 95% CI: 1.273–2.630, P = 0.001), and GCs treatment (OR: 2.721, 95% CI: 2.008–3.686, P < 0.001) were independently related to menstrual disorders [Figure 1].Figure 1: Risk factors of menstrual disorders. ∗P < 0.05. BMI: Body Mass Index; CI: Confidence interval; CYC: Cyclophosphamide; GCs: Glucocorticoids; MMF: Mycophenolate Mofetil; SLE: Systemic lupus erythematosus.Among subjects with pregnancy history, the incidence of preterm delivery, miscarriage, fetal growth restriction, placental abruption, and hypertensive disease of pregnancy was 14.05%, 9.95%, 7.87%, 4.40%, and 2.26%, respectively [Supplementary Table 2, https://links.lww.com/CM9/B404]. There were no significant differences in age (34.83 ± 6.71 vs. 34.50 ± 6.61 years, P = 0.326), BMI (22.11 ± 3.18 vs. 22.21 ± 3.40 kg/m2, P = 0.558), disease duration (6.43 ± 5.37 vs. 6.06 ± 5.03 years, P = 0.146), history of CYC treatment (39.46% vs. 40.27%, P = 0.770), GCs treatment (73.70% vs. 72.86%, P = 0.739), or history of MMF treatment (38.00% vs. 35.15%, P = 0.295) between patients with and without APO [Supplementary Table 3, https://links.lww.com/CM9/B404]. Of the 1250 births in women, 70.48% were full-term normal births, 19.44% were born prematurely, 8.96% were small for gestational age neonates, 7.76% had neonatal pathological jaundice, and 1.44% had neonatal lupus. Patients in the ABO group were younger (32.59 ± 5.57 vs. 34.73 ± 6.52 years, P < 0.001) and experienced longer disease duration (7.53 ± 5.66 vs. 6.18 ± 5.02 years, P < 0.001) than patients without ABO. History of CYC treatment (24.39% vs. 48.03%, P < 0.001), GCs treatment (48.79% vs. 100%, P < 0.001), and MMF treatment (16.80% vs. 52.49%, P < 0.001) were significantly lower in the ABO group [Supplementary Table 4, https://links.lww.com/CM9/B404]. Binary logistic regression demonstrated that age (OR: 0.951, 95% CI: 0.912–0.991, P = 0.017) might be a protective factor associated with ABO. We conducted a large, cross-sectional study that investigated menstrual irregularity, pregnancy outcomes, and birth outcomes in SLE patients in China, and the results revealed that >75% of SLE patients experienced menstruation irregularity. Risk factors for menstrual irregularity included age, CYC treatment, and GCs treatment. This study found that age, BMI, disease duration, and treatment were not significantly associated with APO. The CYC, MMF, and GCs treatment may be associated with a low prevalence of ABO. Menstrual irregularity is common in SLE patients. In this study, nearly 50% of the patients experienced light menstrual bleeding, >20% of patients experienced shortened menstrual bleeding, and 10% experienced amenorrhea. This is consistent with previous studies.[4,5] Additionally, premature ovarian failure is associated with specific SLE-related autoantibodies (anti-Sm, anti-RNP, anti-cardiolipin, and lupus anticoagulant) and the use of immunosuppressants, particularly the use of CYC.[6,7] This study indicates that CYC treatment might be a risk factor for menstrual irregularity. Women with SLE have poorer maternal-fetal outcome compared with healthy individuals.[8] The rate of fetal loss has ranged from 3% to 43%. The rate of fetal loss in SLE pregnancies has decreased from an average of 43% to 17% over the past 40 years.[9] Disease flares, pregnancy loss, preeclampsia, preterm delivery, and intrauterine growth restrictions remain the primary complications during pregnancy.[10] This study has some limitations. It is a cross-sectional observational study that is unable to identify a clear cause–effect relationship. Additionally, the questionnaire could result in time, selection, recall, and reporting bias. At the same time, the timing of medication administration was unclear, which was a limitation of our study. However, this study included a large number of multicenter SLE patients, which helped avoid selection bias. Despite these limitations, the results of our study represent the current status of SLE patients in China. In conclusion, female SLE patients of childbearing age have a high proportion of menstrual abnormalities, APO, and ABO. Acknowledgements We would like to thank all the rheumatologists, gynecologists, and patients that participated in this study. We were especially grateful to an out-of-hospital patient management platform called "MIJIAN." Funding This study was supported by grants from the research project from the Beijing Natural Science Foundation (No. 7192211) and China International Medical Foundation (No. Z-2018-40-2101).
As it becoming more and more reliable and mature, the technology of face recognition has been widely applied to nowadays life. However, conventionally, face recognition uses the visible light as the imaging spectrum and is thus limited under lighting conditions (such as nighttime) and bad atmospheric conditions (such as rain, fog). Infrared face imaging provides an alternative solution to above problem. Nonetheless, infrared (IR) facial images are usually in low quality due to limitation of current imaging devices as well as atmospheric noises and disturbance. This situation restrains the face recognition system from performing well. Therefore, enhancing of low-quality IR facial images is crucial to a practical IR face recognition system. We in this research work propose to address the problem of IR facial image enhancement by a succession of IR facial denoising and IR facial deblurring. The former is realized via a deep neural network of denoising while the latter is achieved by a blind deconvolution algorithm. The denoising DNN is trained on the Waterloo Exploration database and tested on our multispectral face dataset. The metrics of PSNR and running time are used to compare between different denoising methods including both traditional ones and deep learning-based ones. The metric of Tenegrad is used to evaluate the deblurring method involved. Overall, image quality is improved significantly, which in turn proves our proposed framework of successive IR face enhancement to be beneficial.
To evaluate associations between bone destruction markers and musculoskeletal ultrasonography (MU) findings in patients with gout and hyperuricaemia and clarify the role of MU in treatment responsiveness.One-hundred and fifty patients with gout and 100 patients with hyperuricaemia were divided into five groups according to MU manifestations. Circulating Dickkopf-1 (DKK-1) and receptor activator of nuclear factor-κB ligand (RANKL) levels were measured. Thirty patients from the gout group and 10 from the hyperuricaemia group, were treated for 1 year with urate-lowering therapy (ULT).Patients with gout and tophus and/or bone erosion had the highest DKK-1 and RANKL levels. Patients with gout and MU-evidenced aggregates and/or double-contour signs had higher DKK-1 and RANKL levels than the normal MU group (p<0.001). Patients with hyperuricaemia and abnormal MU findings had significantly higher DKK-1 and RANKL levels than those with normal MU findings. DKK-1 and RANKL levels positively correlated with disease duration in patients with gout (r=0.430, p<0.001; r=0.359, p<0.001, respectively) and hyperuricaemia (r=0.446, p<0.001; r=0.379, p<0.001, respectively). After ULT, MU abnormalities disappeared in 12 and 8 patients with gout and hyperuricaemia, respectively. The largest tophus diameter decreased in patients with gout (t=6.092, p<0.001). DKK-1 and RANKL concentrations significantly decreased in all patients. Lower serum urate levels corresponded with higher ratios of normal MU features in all patients.In patients with gout and hyperuricaemia, MU manifestations were associated with DKK-1 and RANKL levels and were ameliorated after ULT. Thus, MU could be a useful tool in assessing bone remodelling and monitoring disease responsiveness.
Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ± 11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.
AbstractObjectives: To evaluate the relationship between Hydroxychloroquine (HCQ) dosage and the incidence of flares in Systemic Lupus Erythematosus (SLE). Methods: In this retrospective cohort study, 703 SLE patients from multiple sites in China were analyzed from October 2020 to May 2023. Patients with a SLEDAI-2K score ≥4 were categorized into low-dose (≤6.7 mg/kg/day) and high-dose (>6.7 mg/kg/day) HCQ groups. The primary outcome was an SLE flare incidence, determined by therapy augmentation, an SLEDAI-2000 increase of ≥4 points, or hospitalization. Results: Among the 703 patients, 45.5% experienced flares. Patients in the high-dose group had a significantly lower flare incidence (41.1%) compared to the low-dose group (51%, P=0.009). Cox regression analyses showed that higher HCQ doses were consistently associated with a reduced risk of flares (HR 0.93, 95% CI 0.86–0.99, P=0.03). When stratified by HCQ dosage, patients receiving≥6.7mg/kg/day had a lower risk of flares compared to those receiving <6.7mg/kg/day, with a hazard ratio of 0.76 (95% CI 0.61–0.96, P=0.019). Kaplan-Meier survival analysis confirmed a longer flare-free survival in the high-dose group (P=0.022). The smoothed dose HR curve indicated a clear trend of reduced flare risk for increased hydroxychloroquine dosages. Subgroup analyses show a clear trend without significant interaction effects. Conclusions: Higher HCQ dosages are associated with a reduced risk of SLE flares and improved flare-free survival, supporting the optimization of HCQ dosing in SLE management. Keywords: hydroxychloroquine, flare, lupus, systemic
The pathogenesis of rheumatoid arthritis (RA) remains elusive. The initiation of joint degeneration is characterized by the loss of self-tolerance in peripheral joints. Ferroptosis, a form of regulated cell death, holds significant importance in the pathophysiology of inflammatory arthritis, primarily due to iron accumulation and the subsequent lipid peroxidation.The present study investigated the association between synovial lesions and ferroptosis-related genes using previously published data from rheumatoid patients. Transcriptome differential gene analysis was employed to identify ferroptosis-related differentially expressed genes (FRDEGs). To validate FRDEGs and screen hub genes, we used weighted gene co-expression network analysis (WGCNA) and receiver operating characteristic (ROC) curves. Subsequently, immune infiltration analysis and single cell analysis were conducted to investigate the relationship between various synovial tissues cells and FRDEGs. The findings were further confirmed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemical staining, and immunofluorescence techniques.Upon intersecting DEGs with ferroptosis-related genes, we identified a total of 104 FRDEGs. Through the construction of a protein-protein interaction (PPI) network, we pinpointed the top 20 most highly concentrated genes as hub genes. Subsequent analyses using ROC curve and WGCNA validated eight FRDEGs: TIMP1, JUN, EGFR, SREBF1, ADIPOQ, SCD, AR, and FABP4. Immuno-infiltration analyses revealed significant infiltration of immune cell in RA synovial tissues and their correlations with the FRDEGs. Notably, TIMP1 demonstrated a positive correlation with various immune cell populations. Single-cell sequencing date of RA synovial tissue revealed predominant expression of TIMP1 is in fibroblasts. RT–qPCR, immunohistochemistry, and immunofluorescence analyses confirmed significant upregulation of TIMP1 at both mRNA and protein levels in RA synovial tissues and fibroblast-like synoviocytes (FLS).The findings provide novel insights into pathophysiology of peripheral immune tolerance deficiency in RA. The dysregulation of TIMP1, a gene associated with ferroptosis, was significantly observed in RA patients, suggesting its potential as a promising biomarker and therapeutic target.
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