LOX-1 is involved in IL-1β production and extracellular matrix breakdown in dental peri-implantitis

PurposeTo explore whether lectin-type oxidized LDL receptor 1 (LOX-1), interleukin 1 beta (IL-1β), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) are involved in the nosogenesis of human dental peri-implantitis and determine the role of LOX-1 in IL-1β, MMP2 and MMP9 production in response to Porphyromonas gingivalis.MethodsPeri-implant crevicular fluid (PICF) was collected from ten patients with healthy implants and ten patients with peri-implantitis. The LOX-1 protein in PICF was detected by Western-blot, and the expression of LOX-1 in superficial gingiva of peri-implantitis patients was detected by immunofluorescence staining. The IL-1β, MMP2 and MMP9 proteins in PICF were detected by enzyme-linked immunosorbent assay (ELISA). THP-1 macrophages were pretreated with neutralizing antibody (LOX-1) and inhibitors (LOX-1 and c-Jun N-terminal kinase, JNK) to evaluate the role of LOX-1 and JNK in IL-1β production, as well as the role of LOX-1 in MMP2 and MMP9 production in response to P. gingivalis by quantitative polymerase chain reaction (RT-PCR) and Western-blot.ResultsLOX-1, IL-1β, MMP2 and MMP9 increased in PICF of peri-implantitis patients and in THP-1 macrophages on P. gingivalis stimulation. IL-1β, MMP2 and MMP9 production in response to P. gingivalis in THP-1 macrophages was dependent on LOX-1. JNK was responsible for LOX-1 induced IL-1β production as a result of P. gingivalis infection.ConclusionLOX-1 is involved in IL-1β production and extracellular matrix breakdown is a novel inflammatory pathway trigger and potential drug target in human dental peri-implantitis.     

Real-world treatment patterns and outcomes of pyrotinib-based therapy in patients with HER2-positive advanced breast cancer (PRETTY): A nationwide,prospective, observational study

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential.     

MicroRNAs and immune regulatory T cells

MicroRNAs (miRNAs)-mediated RNA interference are emerging as an important regulatory pathway for various biological processes, including development, differentiation, and homeostasis. Accumulated evidence suggests that miRNAs regulate T cell and B cell differentiation, proliferation, and apoptosis. Deletion of miRNAs in hematopoietic stem cells or in thymus disrupts T cell homeostasis and results in autoimmunity and abnormal cytokine production. Regulatory T cells are potent immune regulators. In this mini-review, we provide a brief overview of the important roles of miRNAs in the development and function of T cells, especially in immune regulatory T cells.     

Combined immunotherapy and targeted treatment for primary alveolar soft part sarcoma of the lung: case report and literature review

Investigational New Drugs - Primary acinar soft part sarcoma of the lung (ASPS) is a rare malignancy with unique cellular structure and clinical and genetic characteristics. Most patients do not...     

Risk factors and characteristics of ischemic stroke in patients with immune thrombocytopenia: A retrospective cohort study

ObjectivesPrevious research has found that patients with immune thrombocytopenia (ITP) have an increased risk of thrombosis, such as venous thromboembolism (VT), ischemic stroke (IS)/transient ischemic attack (TIA), and cardiovascular disease (CVD), but the risk factors for stroke in patients with ITP have yet to be determined. This study aims to determine the risk factors and characteristics of ischemic stroke in patients with ITP.Materials and methodsThis study included adults with incident primary ITP diagnosed in a tertiary medical center between 2010 and 2020. The t-test and Mann-Whitney U test were used to compare the variables between IS and non-IS groups, and the multivariate logistic regression model was employed to evaluate correlations.ResultsThe study enrolled 1824 individuals, of whom 17 (0.93%) had IS, and 138 (1:8) were randomly chosen from 1807 non-IS patients. Age was found to be substantially associated with stroke in the multivariate analysis (OR 1.07, 95% CI: 1.026-1.116; p = 0.001). We found no correlation between platelet counts (PLT) (OR 1.013, 95% CI: 0.995-1.033; p = 0.164), mean platelet volume (MPV), platelet larger cell ratio (P-LCR), prothrombin time (PT) (OR 1.455, 95% CI 0.979-2.164; p = 0.064), activated partial thromboplastin time (APTT), D-dimer, fibrinogen or antinuclear antibody (ANA) and stroke. Of 17 ITP-IS patients, 7 (53.8%) were cryptogenic, greater than the general IS population. Three (23.1%) of them had an embolic pattern.ConclusionFor ITP patients, age was a significant predictor of stroke. ITP-IS patients had a more cryptogenic origin, with some showing an embolic pattern.     

经鼻咽窝区桡动脉介入路径在冠脉造影及介入治疗中的经验分析

目的 探讨经鼻咽窝区桡动脉入路行冠脉造影及介入治疗的有效性与安全性。 方法 选取2020年6月～2020年12月在青岛阜外心血管病医院行冠脉造影及介入治疗的199例患者,分为对照组（经腕部近端桡动脉穿刺入路,n = 98）和研究组（经鼻咽窝区桡动脉入路,n = 101）;搜集患者的一般性住院资料、冠心病高危因素、穿刺时间、术后即刻疼痛（NRS）评分、术后3 h（NRS）评分、压迫止血时间、术后并发症等数据。 结果 对照组共成功穿刺近端桡动脉96例,成功率98 %,研究组共成功穿刺鼻咽窝桡动脉96例,成功率95 %;差异无统计学意义;与对照组比较,研究组穿刺时间较长（P<0.01）,术后3 hNRS评分较低（P<0.05）,术后压迫时间较少（P<0.01）,并发症二者差异无统计学意义。 结论 经鼻咽窝区远端桡动脉介入路径行冠脉造影及介入治疗具有可行性、安全性和有效性,且在术后止血时间及术后3 h舒适度方面要优于近端桡动脉入路。     

Rheumatoid arthritis coexisting with ankylosing spondylitis: A report of 22 cases with delayed diagnosis

Coexisting rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in the same patient is often thought to be rare, and thus misdiagnosis is common. The aim of our study was to describe the main characteristics of RA coexisting with AS in patients with delayed diagnoses and improve awareness of the disease association.Between 2012 and 2018, data from 22 patients who had RA and AS (RA/AS) were retrospectively reviewed. All patients had a history of delayed diagnosis for RA or AS. The clinical features and radiographic changes of RA and AS patients were obtained at baseline and after 2 years. Disease activity score 28 (DAS28) or bath ankylosing spondylitis disease activity index (BASDAI) were used as outcome measures. The mean age at the time of diagnosis of RA/AS was 51.8 years, while the mean duration of diagnostic delay was 5.5 years. Middle-aged women were the most common subgroup among the RA/AS cohort. The common clinical manifestations were systemic, symmetric, peripheral, and axial arthritis. The erythrocyte sedimentation rate and C-reactive protein levels in RA/AS patients were elevated at the time diagnosis of RA/AS. The typical radiologic changes for the 2 diseases coexisted in RA/AS patients. The DAS28 and BASDAI scores at the 2-year follow-up evaluation were lower than the initial assessment.Coexisting RA and AS is often misdiagnosed for many years; a lack of recognition of RA and AS together is one of the most common reasons. Systemic, symmetric, peripheral, and axial arthritis in middle-aged women were the most frequent presentations at onset.