Effect of IL-17 on pulmonary artery smooth muscle cells and connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVE: To explore the role of interleukin (IL)-17 in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). METHODS: Enzyme-linked immunosorbent assay (ELISA) were used to compare levels of serum IL-17 in patients with CTD-PAH and healthy controls (HCs). After treatment for 3 months, the serum IL-17 levels were tested in CTD-PAH. ELISA and immunohistochemistry were used to compare levels of serum IL-17 and numbers of pulmonary artery IL-17+ cells, respectively, in a rat model of monocrotaline-induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL-17 for various time periods. Proteins in the mitogen-activated protein kinase (MAPK) pathway were examined by western blot. RESULTS: Levels of IL-17 were upregulated in patients with CTD-PAH compared to HCs. After 3 months of treatment, serum IL-17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL-17 levels and numbers of IL-17+ cells infiltrating lung arterioles were increased in PAH model rats. IL-17 could dose- and time-dependently promote proliferation and migration of PASMCs as well as time-dependently induce IL-6 and intercellular cell adhesion molecule-1 (ICAM-1) expression. The levels of MKK6 increased after IL-17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. CONCLUSION: Levels of IL-17 may increase in CTD-PAH, and IL-17 promotes proliferation, migration, and secretion of IL-6 and ICAM in PASMCs, respectively, which likely involves the p-38 MAPK pathway.

Sex Differences in Clinical Manifestations of Hospitalized Patients With Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Cohort Study.

OBJECTIVE: To investigate the effect of sex on the clinical characteristics, prognoses, and therapeutic selection of eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We retrospectively enrolled 170 hospitalized patients with EGPA who were managed at our hospital between 2007 and 2020. Detailed clinical data were reviewed. Manifestations, prognoses, treatments, and outcomes were compared between female and male patients. Cumulative survival rates were calculated using Kaplan-Meier curves. RESULTS: In this cohort, the male to female ratio was 1.4:1. Renal involvement was more frequent in male patients, including serum creatinine elevation, and proteinuria > 1 g/24 h. Severe gastrointestinal (GI) involvement occurred more commonly in male patients. Female patients had longer allergy duration and higher ratios of allergic rhinitis and asthma. Sex differences in proteinuria > 1 g/24 h, serum creatinine > 150 mmol/L, severe GI involvement, and weight loss were more significant in patients aged ≤ 55 years than those in patients aged > 55 years. Overall, male patients had a higher Birmingham Vasculitis Activity Score and a worse prognosis assessed at diagnosis, with a lower proportion of 1996 Five Factor Score = 0 than females. Regarding treatment selection, methylprednisolone pulse and cyclophosphamide were administered more frequently to male patients. All-cause mortality and cumulative survival rates were comparable between the sexes. CONCLUSION: In this Chinese EGPA cohort, male and female patients showed distinct disease phenotypes. Male patients with EGPA had a higher disease activity at diagnosis and required more aggressive treatment for remission induction.

Associations between sarcoidosis, autoimmune diseases, and autoantibodies: a single-center retrospective study in China.

To describe the clinical manifestations, immunological features, and risk factors in patients with sarcoidosis complicated with autoimmune diseases (ADs) as well as determine the frequency of autoantibodies and possible correlation between autoantibodies and laboratory data. Patients with pathologically confirmed sarcoidosis at Beijing Chaoyang Hospital (China) between January 2017 and October 2020 were included. Age- and sex-matched patients who visited the rheumatology outpatient clinic without systemic or ADs were included as controls. Demographic, clinical, serological, and radiological data of sarcoidosis patients were recorded and analyzed. To exclude ADs, autoantibodies, such as antinuclear antibody, extractable nuclear antigen antibodies, and anti-cyclic citrullinated peptide antibody were assessed in controls. A total of 154 sarcoidosis patients (111 females; 72.1%) with a mean ± standard deviation age of 50.7 ± 10.3 years were included. Nineteen patients (12.3%) had ADs; Hashimoto's thyroiditis (n = 6) and Sjogren's syndrome (n = 4) were common. Age, globulin, immunoglobulin G, erythrocyte sedimentation rate (ESR), and C-reactive protein were significantly different between sarcoidosis patients with and without ADs. The ESR level might be a risk factor for sarcoidosis complicated with ADs (RR = 1.053; P = 0.018). Autoantibodies were detected in 29 patients (18.8%), and the frequency was significantly higher than that in controls (18.8% vs. 3%; P = 0.001). Sarcoidosis patients were more likely to have autoantibodies despite the absence of ADs (10.4% vs. 3%; P = 0.031). Age may be a risk factor for sarcoidosis patients presenting with autoantibodies (RR = 1.077; P = 0.042). An association was identified between ADs and sarcoidosis. The inflammatory indexes, such as ESR, IgG, and CRP, were significantly different between sarcoidosis patients with and without ADs. ESR might be a risk factor for the coexistence of ADs and sarcoidosis. Sarcoidosis patients were prone to being autoantibody-positive despite the absence of ADs, and age might be a risk factor for sarcoidosis presenting with autoantibodies.

Pulmonary amyloidosis and cystic lung disease in primary Sjögren's syndrome: a case report and literature review.

This study presents a rare case of pulmonary amyloidosis and cystic lung disease associated with primary Sjögren's syndrome. In February 2019, a 76-year-old woman with primary Sjögren's syndrome presented to our rheumatology department for lung problems. Four years before presentation, the patient underwent chest computed tomography that revealed multiple nodules with numerous thin-walled lumen in both lungs. Pulmonary nodulectomy for hemoptysis was performed 2 years before presentation. Pathological findings suggested chronic inflammation of the bronchus and amyloid deposition in the lung tissue. The nodules and vesicles were generally larger from January 2015 to October 2018 when she did not receive any special medication, but the nodules and vesicles tended to be stable from February to August 2019 when she was treated with hydroxychloroquine sulfate regularly, suggesting that hydroxychloroquine sulfate may be helpful in this patient.

Risk factors for progression and prognosis of primary Sjögren's syndrome-associated interstitial lung disease in a Chinese population.

OBJECTIVE: This study explored differences between primary Sjögren's syndrome-associated interstitial lung disease (pSS-ILD) patients with and without ILD progression, and analyzed the factors affecting the progression and prognosis of pSS-ILD. METHODS: This study is a retrospective cohort study which enrolled 113 pSS-ILD patients hospitalized between 2011 and 2017. RESULTS: The 3-year survival rate of the pSS-ILD patients was 91.15%, and the 5-year survival rate was 84.07%. Univariate analysis showed that Raynaud's syndrome, hypoproteinemia, extensive lung involvement, possible usual interstitial pneumonia pattern were risk factors for the progression of ILD in patients with pSS-ILD, and cyclophosphamide was a protective factor for the progression of ILD in patients with pSS-ILD. Multiple logistic regression analysis showed that extensive lung involvement (odds ratio 4.143, 95% CI: 1.203-14.267, P < .05) was an independent risk factor for the progression of pSS-ILD. Cox hazard analysis showed that pSS-ILD with hypoproteinemia (hazard ratio [HR] 17.758, 95% CI: 4.753-66.340, P <- .05) and extensive lung involvement (HR 3.450, 95% CI: 1.419-8.390, P < .05) were associated with worse survival of patients. CONCLUSION: Extensive lung involvement is an independent risk factor for the progression of ILD in patients with pSS-ILD. Hypoproteinemia and extensive lung involvement are independent risk factors for mortality in patients with pSS-ILD, after controlling for potentially influential variables.

Switching from allopurinol to febuxostat: efficacy and safety in the treatment of hyperuricemia in renal transplant recipients.

The aim of this study was to evaluate the efficacy and tolerability of febuxostat in renal transplant recipients who were previously treated with allopurinol (the daily oral dose is 100 mg). A 6-month cohort study was conducted with 46 renal transplant recipients who had hyperuricemia. In 22 patients, treatment was changed from allopurinol to febuxostat (febuxostat was given at an oral dose of 20 mg once a day), and the other 24 patients continued the allopurinol treatment (the daily oral dose is 100 mg). The serum levels of uric acid (UA), creatinine, other biochemical parameters, estimated glomerular filtration rate (eGFR), and adverse events were measured at baseline as well as at 1, 3, and 6 months after the switch to febuxostat. Serum UA levels significantly decreased from 470.82 ± 34.37 to 378.77 ± 51.97 µmol/L in the febuxostat group, and decreased from 469.46 ± 33.47 to 428.21 ± 23.37 µmol/L in the allopurinol group. The eGFR increased from 75.55 to 85.23 mL/min in the febuxostat group, and decreased from 78.79 to 70.31 mL/min in the allopurinol group. In renal transplant recipients, febuxostat reduced the serum UA levels resulting in minor short-term improvement of renal function with no changes in the other biochemical parameters.

Thymic epithelial tumor complicated by immunological abnormalities: results from a single-center retrospective study in China.

BACKGROUND: To describe the clinical manifestations, immunological features, treatments, and outcomes of patients with thymic epithelial tumor (TET) complicated by immunological abnormalities, and to improve knowledge on immunological abnormalities in this rare disease. METHODS: Patients with pathologically confirmed TET at Beijing Chaoyang Hospital between January 2013 and May 2018 were included in this study, and clinical data were analyzed retrospectively. Immunological abnormalities were classified into two groups as follows: Good syndrome (GS) and autoimmune disease (AD). RESULTS: Fifty-nine TET patients were enrolled; twenty-two patients (37.3%) had immune dysfunction. There were no gender, age, or histological type differences between groups with or without immunological abnormalities. Six patients had GS, of whom four patients were diagnosed after thymectomy. Recurrent respiratory infections, particularly opportunistic infections, were the most common manifestation. Three GS patients developed a second cancer (50%; P=0.011). Anti-infective therapy and immunoglobulin supplements effectively treated GS. Seventeen patients developed ADs, including myasthenia gravis (MG) (n=13), Hashimoto's thyroiditis (n=4), Sjogren's syndrome (n=1), rheumatoid arthritis (n=1), pemphigus (n=1), and Evans syndrome (n=1). One patient developed both MG and GS and 4 patients presented with two ADs. Three AD cases occurred after thymectomy. Pemphigus and 80% (8/10) of MG cases were resolved following thymectomy. CONCLUSIONS: There is a strong association between immunological abnormalities and TET, which may present at any time point during the disease, even after thymectomy. In addition to infection, GS patients are more likely to develop a second cancer. Thymectomy may produce favorable outcomes for MG in this study, while surgery does not improve immunodeficiency in GS patients.

Breast panniculitis with liquefactive fat necrosis: A case report.

Panniculitis is a group of heterogeneous disorders characterized by inflammation of the subcutaneous adipose tissue. Panniculitis of breast tissue as the initial manifestation has rarely been reported and is often misdiagnosed. Breast panniculitis may cause substantial morbidity and early diagnosis and treatment are important for the prognosis of the disease. The present study has reported a case of panniculitis with inflammation of the mammary glands as the initial presentation and provided a detailed description of ultrasonography, X-ray, computed tomography, magnetic resonance imaging and other imaging features of breast panniculitis. The treatment and follow-up were also described. Following treatment with systemic corticosteroids combined with methotrexate and thalidomide for 2 months, the breast appeared to be normal without scar formation. The present case report provides a good reference for the future diagnosis and treatment of breast panniculitis.

Risk factors and treatment of pneumothorax secondary to granulomatosis with polyangiitis: a clinical analysis of 25 cases.

OBJECTIVES: To investigate the risk factors and treatment strategies for pneumothorax secondary to granulomatosis with polyangiitis (GPA). METHOD: Retrospective analysis of cases with pneumothorax secondary to GPA from our own practice and published on literature. RESULTS: A total of 25 patients, 18 males and 7 females, mean age 44 ± 15.7 years, were analyzed. Diagnosis included pneumothorax (11 cases), hydropneumothorax (n = 5), empyema (n = 8) and hemopneumothorax (n = 1). 88% (22/25) patients showed single/multiple pulmonary/ subpleural nodules with/without cavitation on chest imaging. Erythrocyte sedimentation rate and C-reactive protein were both elevated. Corticosteroids and immunosuppressive agents were used in 16 cases. Five cases received steroid pulse therapy, of which 4 patients survived. Pleural drainage was effective in some patients. Seven patients underwent surgical operations. In the 10 fatal cases, infection and respiratory failure were the most common cause. Lung biopsy/ autopsy showed lung/pleural necrotizing granulomatous vasculitis, breaking into the chest cavity, pleural fibrosis, bronchial pleural fistula, etc. The mean age in the death group was greater than the survival group (53 ± 12.9 years vs 40.1 ± 14.7 years, p = 0.05), the ineffective pleural drainage was also higher in the death group (5/5 vs 0/7, p = 0.01). CONCLUSIONS: Pneumothorax was seen in the active GPA, due to a variety of reasons, and gave rise to high fatality rate. Aggressive treatment of GPA can improve the prognosis. Older and lack of response for pleural drainage indicates poor prognosis.

A rare case of meningoencephalitis by Listeria monocytogenes in systemic lupus erythematosus: case report and review.

Patients with systemic lupus erythematosus (SLE) have a high risk of infection. Central nervous system infection and neuropsychiatric SLE are both major causes of death. It is vital to distinguish between these two conditions to improve prognosis due to the treatment paradigms required for each condition. Here, we report one case of meningoencephalitis by Listeria monocytogenes (LM) in a patient with SLE who presented with fever and developed headache and altered in consciousness in the hospital. The cerebrospinal fluid culture was positive for LM, and magnetic resonance imaging (MRI) findings were suggestive of ependymitis and periventricular white matter lesions. Amoxicillin/sulbactam, trimethoprim-sulfamethoxazole, and rifampicin were administered for 8 weeks. The patient had a relative good recovery without serious neurological sequelae after a follow-up of nearly 2 years. MRI abnormalities also had obvious resolution.

Successful treatment of granulomatosis with polyangiitis with hydropneumothorax using corticosteroids and immunosuppressant.

Pneumothorax and pleural effusion is a rare and serious complication of granulomatosis with polyangiitis (GPA). The present study reported a case with a history of sinusitis for 20 years, dry cough for three years and exacerbated purulent nasal discharge and recurrent skin ulcers for two years. The patient experienced sudden difficulty in breathing two months prior to presentation. Lung computed tomography (CT) showed multiple bilateral lung nodules and cavitary nodules as well as right hydropneumothorax. Paranasal sinus CT showed soft tissue infiltration. The cytoplasmic pattern of anti-neutrophil cytoplasmic antibody (c-ANCA) was positive and anti-proteinase 3 (PR3) antibodies, erythrocyte sedimentation rate and C-reactive protein were elevated. After pleural drainage and methylprednisolone pulse treatment, followed by cyclophosphamide and cyclosporine, the patient's symptoms were ameliorated, lungs were re-expanded, and c-ANCA, PR3 and inflammatory markers returned to normal levels.

Evaluating osteoporotic fracture risk with the Fracture Risk Assessment Tool in Chinese patients with rheumatoid arthritis.

This study aims to evaluate the discriminative and predictive capacity of the Fracture Risk Assessment Tool (FRAX) to determine the 10-year risk of osteoporotic fracture in Chinese rheumatoid arthritis (RA) patients.This study included 168 RA patients and 168 healthy individuals as controls. The Chinese mainland FRAX model was applied to calculate the 10-year risk of osteoporotic fractures, defined as fracture of the spine, forearm, hip, or shoulder.The incidence of osteoporosis was significantly increased in RA patients compared to controls (P < .05). Bone mineral density (BMD), lumbar vertebra T-score, and femoral neck T-score were significantly lower in RA patients compared to controls (P < .05). BMD, disease duration, DAS28, and glucocorticoid use were important risk factors for osteoporotic fractures in Chinese RA patients. Ten-year osteoporotic fracture risk in Chinese RA patients was higher when BMD was incorporated in FRAX.There was a higher incidence of osteoporosis and reduced BMD in RA patients compared to controls. The FRAX model should integrate femoral neck BMD with other risk factors to evaluate osteoporotic fracture risk in RA patients, making it a valuable screening tool.

Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout.

We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P < 0.05). After 4-, 12-, and 24-week febuxostat treatments, UA and hs-CRP concentrations were significantly lower than baseline (P < 0.05). INS and HOM-IR decreased slightly after a 4-week treatment with febuxostat but declined significantly after 12 and 24 weeks of treatment. Importantly, hs-CRP values positively correlated with those of HOMA-IR (r = 0.353, P = 0.018) and INS (r = 0.426, P = 0.034). Our findings confirm that IR exists in gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.

[Clinical Efficacy and Safety of Rituximab Combined with Fludarabine and Cyclophosphamide for Treatment of Chronic Lymphocytic Leukemia].

OBJECTIVE: To explore the clinical efficacy and safety of rituximab combined with fludarabine and cyclophosphamide for the treatment of the chronic lymphocytic leukemia (CLL). METHODS: Forty cases of CLL patients treated in our hospital from March 2010 to March 2014 years were selected and divided into the observation group (20 cases) and control group (20 cases) by random number table method. The patients in control group were treated with CHOP chemotherapy, the patients in observation group were treated with rituximab combined with fludarabine, cyclophosphamide treatment. The therapeutic efficacy of patients in 2 groups was analyzed according to the peripheral hemogram indexes, symptom and sign disappeared time as well as adverse reaction incidence. RESULTS: the remission rate in observation group was 90.00%, which was significantly higher than that in control group (70.00%) (P < 0.05); the peripheral hemogram indexes in 2 groups before treatment showed no significant difference (P > 0.05), and were significantly improved after treatment, but the white blood cell count and lymphocyte absolute number were significantly lower in observation group as compared to the control group (P < 0.05); symptom and sign disappeared time in observation group were significantly shorter as compared with the control group (P < 0.05); adverse reaction incidence in obseovation group was significantly lower as compared with control group (P < 0.05). CONCLUSION: application of rituximab combined with fludarabine and cyclophosphamide in the treatment of CLL shows the higher curative effect, can effectively improve the symptoms and reduce the incidence of adverse reactions. It is worthy to be popularized.

[Long-term effects of hydroxychloroquine on metabolism of serum lipids and left ventricular structure and function in patients of systemic lupus erythematosus].

OBJECTIVE: To observe the long-term effects of hydroxychloroquine treatment on blood lipids and left ventricular function of systemic lupus erythematosus (SLE) patients. METHODS: A total of 72 SLE patients were randomly divided into 2 groups of hydroxychloroquine treatment (n = 36) and non-hydroxychloroquine (n = 36). The serum level of lipids, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), fractional shortening rate (FS), left ventricular ejection fraction (LVEF) and E/A ratio were measured before, 6 month, 12 month and 2 years after treatment. RESULTS: After long-term use of hydroxychloroquine, there were statistically differences in the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). And LVEDD, LVWPT and E/A were statistically different (P < 0.05) before and after hydroxychloroquine dosing. CONCLUSION: The long-term use of hydroxychloroquine may improve lipid metabolism and left ventricular function in SLE patients.