CD147 regulates the formation and function of immune synapses.

CD147 is a T cell activation-associated molecule which is closely involved in the formation of the immune synapse (IS). However, the precise role of CD147 in T cell activation and IS formation remains unclear. In the present study, we demonstrated that CD147 translocated to the IS upon T cell activation and was primarily distributed in the peripheral super molecular cluster (p-SMAC). The knock down of CD147 expression in T cells, but not in B cells, impaired IS formation. CD147 participated in IS formation between T cells and different types of antigen-presenting cells (APCs), including macrophages and dendritic cells. Ligation of CD147 with its monoclonal antibody (mAb) HAb18 effectively inhibited T cell activation and IL-2 secretion. CD98, a critical molecule interacting with CD147, was distributed in IS in a CD147-dependent way. Phosphorylation levels of T cell receptor (TCR) related molecules, like ZAP-70, ERK, and cJun, were down-regulated by CD147 ligation, which is crucial for the interaction of CD147 and TCR signaling transduction. CD147 is indispensable for the formation of immune synapses and plays an important role in the regulation of its function.

Legacy of herbicides in water from Hailun City, Northeast China: Occurrence, source, and ecological risk assessment.

Herbicides (HBCs) are extensively used in modern agriculture. However, their potential negative impacts on environmental media have emerged as a significant environmental concern. In this study, we employed positive matrix factorization (PMF) to identify the potential sources of HBCs. Furthermore, we utilized a multi-matrix ecological risk model to assess the risks associated with HBCs in both surface water and groundwater in the black soil region of Northeast China. The findings revealed that the levels of ∑15HBCs in surface water and groundwater ranged from 585.84 to 6466.96 ng/L and 4.80 to 11,774.64 ng/L, respectively. The PMF results indicated that surface runoff and erosion accounted for 50% of the total HBCs in water, serving as the primary sources. All tested HBCs exhibited acute risk values within acceptable levels. The risk index for the ∑15HBCs was categorized as "moderate risk" in 31% of the surface waters and 13% of the groundwaters. However, 4% of the groundwater sampling sites reached the "high risk" level. The chronic risk quotient of ∑15HBCs in surface water and groundwater was 92% and 62% at the "high risk" level, respectively. Interestingly, non-carcinogenic HBCs contributed more significantly to the ecotoxicology of the aquatic system than carcinogenic HBCs. This study provides comprehensive information on the legacy of HBCs in water bodies and emphasizes the potential risks posed by HBCs to aquatic systems. The results obtained from this study could help relevant management authorities in developing and implementing effective regulations to mitigate the ecological and environmental risks associated with HBCs.

Automatic quantification and grading of hip bone marrow oedema in ankylosing spondylitis based on deep learning.

OBJECTIVE: This study has developed a new automatic algorithm for the quantificationy and grading of ankylosing spondylitis (AS)-hip arthritis with magnetic resonance imaging (MRI). METHODS: (1) This study designs a new segmentation network based on deep learning, and a classification network based on deep learning. (2) We train the segmentation model and classification model with the training data and validate the performance of the model. (3) The segmentation results of inflammation in MRI images were obtained and the hip joint was quantified using the segmentation results. RESULTS: A retrospective analysis was performed on 141 cases; 101 patients were included in the derived cohort and 40 in the validation cohort. In the derivation group, median percentage of bone marrow oedema (BME) for each grade was as follows: 36% for grade 1 (<15%), 42% for grade 2 (15-30%),and 22% for grade 3 (≥30%). The accuracy of 44 cases on 835 AS images was 85.7%. Our model made 31 correct decisions out of 40 AS test cases. This study showed that THE accuracy rate 85.7%. CONCLUSIONS: An automatic computer-based analysis of MRI has the potential of being a useful method for the diagnosis and grading of AS hip BME.

Astragalus membranaceus (Fisch.) Bunge repairs intestinal mucosal injury induced by LPS in mice.

BACKGROUND: Astragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The purpose of the study was to investigate the curative effects of the decoction obtained from Astragalus membranaceus root in intestinal mucosal injury induced by LPS in mice. An LPS-induced intestinal mucosal injury mice model was applied in the study. METHODS: The mice were post-treated with Astragalus membranaceus decoction (AMD) for 4 days after 3 days LPS induction. ELISA kit was used to detect the content of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4,IL-6 and IL-8 in the serum of each group mice. The morphological changes in intestinal mucosa at the end of the experiments were observed. Both VH (villus height) and CD (crypt depth) were measured using H&E-stained sections. RESULTS: There were significant differences in IL-1ß, IL-4,IL-6, IL-8 and TNF-α levels in AMD-treated group on the 7th day compared to the controls group. The VH was lower in duodenum, jejunum and the ileum in LPS-treated mice compared to the control animals. Similarly, there was also decrease in V/C. Compared to the control mice, for AMD-treated mice, VH and CD had no significantly differences. CONCLUSIONS: Astragalus membranaceus reduced intestinal mucosal damage and promoted tissue repair by inhibiting the expression of inflammatory cytokine.

CD147 up-regulates calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils via a TRPM-7-mediated mechanism.

OBJECTIVES: We aimed to investigate whether CD147 can up-regulate the chemotactic, adhesive and invasive properties of human neutrophils and to determine the mechanism underlying this process. METHODS: Human promyelocytic leukaemia cells (HL-60) cells and peripheral blood or synovial fluid neutrophils were isolated from RA patients. Under cyclophilin A (CypA) stimulation, chemotaxis, adhesion potential and invasion ability were assessed using chemotaxis, adhesion and invasiveness assays. Lipid raft isolation and western blot were used to determine the mechanism underlying the effects of CypA stimulation. RESULTS: CD147 up-regulates the calcium-induced chemotaxis, adhesion ability and invasiveness of human neutrophils in RA patients. Transient receptor potential melastatin 7 may be responsible for this phenomenon. CONCLUSION: These findings suggest that in RA patients, abundant CypA up-regulates the calcium-induced chemotactic, adhesive and invasive properties of neutrophils via direct binding to CD147. Cyclophilin-CD147 interactions might contribute to the destruction of cartilage and bone in RA.

Exploring physical function and physical activity in axial spondyloarthritis: Beyond clinical remission or low disease activity.

OBJECTIVES: To investigate the crucial roles of physical function (PF) and physical activity (PA) in axial spondyloarthritis (axSpA) patients, as well as their correlation with disease activity (DA), and to explore the influence of general characteristics among them. METHODS: We enrolled axSpA patients from Xijing Hospital, spanning March 2022 to August 2022. Spearman rank correlation coefficients were used to assess correlations between PA (measured by the Global Physical Activity Questionnaire [GPAQ]), PF (measured by the Assessment of Spondyloarthritis international Society Health Index [ASAS-HI], the Short Form 36-Item Health Survey [SF-36], and the Bath Ankylosing Spondylitis Functional Index [BASFI]), DA, and their influencing factors. A Mann-Whitney U-test and Kruskal-Wallis H-test were used to compare variables between different patients grouped by sex, human leukocyte antigen B27 (HLA-B27), hip involvement, and intensity of PA and DA. RESULTS: Three hundred fifty-five axSpA patients were included. We observed a moderate to strong correlation between DA and PF in axSpA patients. PA was weakly correlated with DA or PF. DA varied significantly at different PA levels, and patients with low PA levels had poorer PF. Active patients had worse PF, less transport-related PA, and a higher rate of hip involvement with a worse Harris Hip Score (HHS). CONCLUSIONS: We identified a close relationship between DA, PF, and PA in axSpA patients. Further, gender, HLA-B27, and hip involvement affected the clinical manifestation of axSpA patients. These findings demonstrate that clinical remission of axSpA patients requires a comprehensive assessment rather than a single remission of DA.

Prediction of prognosis in patients with systemic sclerosis based on a machine-learning model.

OBJECTIVE: The clinical manifestations of systemic sclerosis (SSc) are highly variable, resulting in varied outcomes and complications. Diverse fibrosis of the skin and internal organs, vasculopathy, and dysregulated immune system lead to poor and varied prognoses in patients with SSc subtypes. Therefore, this study aimed to develop a personalized tool for predicting the prognosis of patients with SSc. METHODS: A cohort of 517 patients with SSc were recruited between January 2009 and November 2021 at Xijing Hospital in China, and 266 patients completed the follow-up and performed in the survival analysis. Risk factors for death were identified using Cox survival analysis and random survival forest-based machine-learning methods separately. The consistency index, area under the curve (AUC), and integrated Brier scores were used to compare the predictive performance of the different prognostic models. RESULTS: The results of Cox-based multivariate regression analysis suggested that pulmonary arterial hypertension, digital ulcer, and Modified Rodnan Skin Score (mRSS) were independent risk factors for poor prognosis in patients with SSc and significant risk factors in random survival forest (RSF) surveys. A nomogram was plotted to evaluate the prognostic risk to facilitate clinical assessment; the RSF model had better predictive performance than the Cox model, with 3- and 5-year AUCs of 0.74 and 0.78, respectively. CONCLUSION: Machine-learning models can help us better understand the prognosis of patients with SSc and comprehensively evaluate the clinical characteristics of each individual. The early identification of the characteristics of high-risk patients can improve the prognosis of those with SSc. Key Points • Regarding predictive performance, the random survival forest model was more effective than the Cox model and had unique advantages in analyzing nonlinear effects and variable importance. • Machine learning using the simple clinical features of patients with systemic sclerosis (SSc) to predict mortality can guide attending physicians, and the early identification of high-risk patients with SSc and referral to experts will assist rheumatologists in monitoring and management planning.

CD147 induces angiogenesis through a vascular endothelial growth factor and hypoxia-inducible transcription factor 1α-mediated pathway in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory and angiogenic disease. However, the molecular mechanisms that promote angiogenesis in RA have not been clearly identified. Our objective was to study the role of CD147 in angiogenesis and determine whether the strategy in which CD147 is suppressed might be useful in reducing angiogenesis in RA. METHODS: Correlations among expression levels of CD147, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1α (HIF-1α) were determined by immunohistochemistry staining. RA fibroblast-like synoviocytes (FLS) cells were cultured under various conditions, and the production of VEGF and HIF-1α was examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The SCID mouse coimplantation model of RA (SCID-HuRAg) was established, mice were treated with CD147 monoclonal antibody, infliximab, or both CD147 and infliximab, and the volume of the grafts and the average vascular density were measured and analyzed. Western blot analyses were performed to examine the potential signaling pathways. RESULTS: The expression levels of CD147 showed significantly positive correlations with VEGF and HIF-1α levels, as well as with vascular density, in RA synovium. After small interfering RNA transfection or after addition of specific antibodies for CD147, the production of VEGF and HIF-1α were significantly reduced. The expression of VEGF and HIF-1α decreased more after CD147 inhibition than after infliximab treatment in the engrafted tissues in SCID-HuRAg mice. The phosphatidylinositol 3-kinase/Akt pathway may be involved in this process. CONCLUSION: CD147 induces up-regulation of VEGF and HIF-1α in RA FLS, further promotes angiogenesis, and leads to the persistence of synovitis. Inhibition of CD147 may be a promising target for novel therapeutic strategies.

Network pharmacology-based analysis on geniposide, a component of gardenia jasminoides, beneficial effects to alleviate LPS-induced immune stress in piglets.

Geniposide is the main medicinal component of Gardenia jasminoides, and its content is approximately 3-8% depending on its origin. Geniposide is a class of cyclic enol ether terpene glucoside compounds with strong antioxidant, free radical quenching and cancer-inhibiting activities. Many studies have reported that geniposide has hepatoprotective, cholestatic, neuroprotective, blood sugar and blood lipid regulation, soft tissue damage treatment, antithrombotic, antitumor and other effects. As a traditional Chinese medicine, gardenia, whether used as gardenia alone, as the monomer geniposide or as the effective part of cyclic either terpenoids, has been reported to have anti-inflammatory effects when used in the right amounts. Recent studies have found that geniposide has important roles in pharmacological activities such as anti-inflammation activity, inhibition of the NF-κB/IκB pathway, and cell adhesion molecule production. In this study, we predicted the anti-inflammatory and antioxidant effects of geniposide in piglets through network pharmacology based on the LPS-induced inflammatory response-regulated signaling pathway. The effects of geniposide on changes in inflammatory pathways and cytokine levels in the lymphocytes of inflammation-stressed piglets were investigated using in vivo and in vitro models of piglet lipopolysaccharide-induced oxidative stress. Network pharmacology identified 23 target genes, of which the main pathways of action were lipid and atherosclerosis, fluid shear stress and atherosclerosis, and Yersinia infection. The main relevant target genes were VEGFA, ROCK2, NOS3, and CCL2. Validation experiments showed that the interventional effects of geniposide reduced the relative expression of NF-κB pathway proteins and genes, restored the expression of COX-2 genes to normal levels, and increased the relative expression of tight junction proteins and genes in IPEC-J2 cells. This indicates that the addition of geniposide can alleviate inflammation and improve the level of cellular tight junctions.

Progressive pseudorheumatoid dysplasia involving a novel WISP3 mutation and sacroiliac and hip arthritis: A case report and literature review.

INTRODUCTION: Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive genetic disease caused by mutations in the Wnt1-inducible signaling pathway protein 3 gene. PPRD is considered a noninflammatory disease, and involvement of the sacroiliac joint and hip arthritis have not been reported previously. PATIENT CONCERNS: We report a case of PPRD in an 11-year-old boy, who presented with bilateral pain and swelling in the knees, elbows, and ankles, and bilateral pain without swelling in the shoulders, wrists, knuckles, and proximal and distal interphalangeal joints for the past 5 years. He had been misdiagnosed with juvenile idiopathic arthritis for more than 6 years. DIAGNOSIS: The correct PPRD diagnosis was made using whole-exome sequencing for Wnt1-inducible signaling pathway protein 3 gene mutations (c.589 + 2T>C and c.721T>G; both mutations have rarely been reported) and magnetic resonance imaging examination; moreover, the latter showed inflammation of the sacroiliac joint and hip joint. INTERVENTION: The patient was administered supplemental calcium, active vitamin D, and glucosamine sulfate. OUTCOME: The patient experienced alleviation of joint pain following treatment initiation; however, joint motion improvement was not obvious. Above all, the long-term use of biologic or targeted synthetic disease-modifying antirheumatic drugs in the future was avoided. CONCLUSION: The findings of the inflammatory aspects in PPRD will enrich our understanding of this rheumatological disease.

Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia.

Our object was to examine how the pre- and post-pandemic COVID-19 impacted the care of acute ST-segment elevation myocardial infarction (STEMI) patients in county hospitals. Using January 20, 2020, as the time point for the control of a unique coronavirus pneumonia epidemic in Jieshou, 272 acute STEMI patients were separated into pre-epidemic (group A, n = 130) and epidemic (group B, n = 142). There were no significant differences between the two groups in terms of mode of arrival, symptom onset-to-first medical contact time, door-to-needle time, door-to-balloon time, maximum hypersensitive cardiac troponin I levels, and in-hospital adverse events (P > 0.05). Emergency percutaneous coronary intervention (PCI) was much less common in group B (57.7%) compared to group A (72.3%) (P = 0.012), and the proportion of reperfusion treatment with thrombolysis was 30.3% in group B compared to 13.1% in group A (P < 0.001). Logistic regression analysis showed that age ≥76 years, admission NT-proBNP levels ≥3,018 pg/ml, and combined cardiogenic shock were independent risk factors for death. Compared with thrombolytic therapy, emergency PCI treatment further reduced the risk of death in STEMI. In conclusion, the county hospitals treated more acute STEMI with thrombolysis during the COVID-19 outbreak.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Investigation and Analysis of Anxiety and Quality of Life among Systemic Lupus Erythematosus Patients in Northwestern China.

The aim of this study was to provide targeted psychological support and effective nursing for systemic lupus erythematosus (SLE) patients. SLE is a complex, systemic autoimmune disease characterized by recurrent episodes and the involvement of multiple organs. With improvements in SLE treatment and the corresponding increase in patients' survival time, the quality of life (QoL) of SLE patients has become an important indicator for evaluating the effectiveness of clinical treatments. To explore the anxiety states and health-related QoL of SLE patients, 106 SLE patients were asked to provide responses for the short-form 36 health survey (SF36), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Visual Analog Scale(VAS). Additionally, the Systemic Lupus Collaborative Clinics Damage Index (SDI) was analyzed. Data regarding patients' age, gender, education level, occupation, family income, and duration of disease were collected. Regression analysis was performed to identify factors related to patients' health-related QoL. For the SF36, the mental components score (MCS), mental health (MH), and bodily pain (BP) occupied dominant positions. Additionally, the MH domain was significantly associated with anxiety in SLE patients. Negative relationships were identified between irregular sleep and the scores for role limitations due to physical problem (RP), vitality (VT), and role limitations due to emotional problem (RE) domains. From the analysis of SLEDAI and SDI scores, anxiety among SLE patients was mainly affected by disease activity and quality of life. This study provides a preliminary understanding of the QoL of SLE patients in western China and highlights the need for the future development of strategies to provide targeted psychological support and effective nursing for SLE patients, in order to improve patients' self-awareness, mental health, and QoL.

Case report: Kimura's disease with minimal degenerative glomerulopathy without eosinophil infiltration responds to mycophenolate mofetil treatment.

Kimura's disease (KD) is a rare chronic progressive immune inflammatory disease. The etiology is unknown and manifests as a chronic inflammatory process, which is more common in young Asian men. The clinical manifestations are painless subcutaneous swelling of the head and neck and periauricular lymphadenopathy, which is slow growing and has a benign course. KD may involve the kidney, and pathological examination revealed eosinophil infiltration in the renal tissue. Proteinuria has been reported in 12-16% of KD cases, and about 60-70% of KD patients will develop nephrotic proteinuria. KD is easily confused with nephrotic syndrome, because KD does not have specific clinical manifestations, laboratory and imaging, and early misdiagnosis is easy. We report a case of KD that was biopsy-proven to have minimal lesion glomerulopathy after ~11 years. In this report, we describe a clinical case of KD with nephrotic syndrome, but there's no eosinophil infiltration in the kidneys. The clinical manifestations of KD recurrence were bilateral eyelid edema, bilateral lower limb swelling, and massive proteinuria in response to mycophenolate mofetil treatment (1.5 g).

Expression of CD147 (EMMPRIN) on neutrophils in rheumatoid arthritis enhances chemotaxis, matrix metalloproteinase production and invasiveness of synoviocytes.

The occurrence of neutrophils at the pannus-cartilage border is an important phenomenon for understanding the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are predominant enzymes responsible for the cartilage degradation. The present article studied the expression of CD147 on neutrophils and its potential role in neutrophil chemotaxis, MMPs production and the invasiveness of fibroblast-like synoviocytes (FLS). The results of flow cytometry revealed that the mean fluorescence intensity of CD147 expression on neutrophils of peripheral blood from RA patients was higher than that in healthy individual. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using chemotaxis assay and it was found that the addition of anti-CD147 antibody significantly decreased the chemotactic index of the neutrophils. Significantly elevated release and activation of MMPs were seen in the co-culture of neutrophil and FLS compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays were also observed in the co-cultured cells. The addition of anti-CD147 antibody had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture model. Our study demonstrates that the increased expression of CD147 on neutrophils in RA may be responsible for CyPA-mediated neutrophil migration into the joints, elevated MMPs secretion and cell invasion of synoviocytes, all of which may contribute to the cartilage invasion and bone destruction of RA. Better knowledge of these findings will hopefully provide a new insight into the pathogenesis of RA.

Preparation and preliminary cytocompatibility of magnesium doped apatite cement with degradability for bone regeneration.

In the present study, we fabricated magnesium doped apatite cement (md-AC) with rapid self-setting characteristic by adding the mixed powders of magnesium oxide and calcium dihydrogen phosphate (MO-CDP) into hydroxyapatite cement (HAC). The results revealed that the md-AC with 50 wt% MO-CDP could set within 6 min and the compression strength could reach 51 MPa after setting for 1 h, indicating that the md-AC had highly initial mechanical strength. The degradability of the md-AC in Tris-HCl solution increased with the increase of MO-CDP amount, and the weight loss ratio of md-AC with 50 wt% MO-CDP was 57.5 wt% after soaked for 12 weeks. Newly flake-like apatite could be deposited on the md-AC surfaces after soaked in simulated body fluid (SBF) for 7 days. Cell proliferation ratio of MG(63) cells on md-AC was obviously higher than that of HAC on days 4 and 7. The cells with normal phenotype spread well on the md-AC surfaces and attached intimately with the substrate, and alkaline phosphatase (ALP) activity of the cells on md-AC significantly improved compared with HAC on day 7. The results demonstrate that the md-AC has a good ability to support cell proliferation and differentiation, and indicate a good cytocompatibility.

Association Between High-Sensitivity Troponin T on Admission and Organ Dysfunction During Hospitalization in Patients Aged 80 Years and Older with Hip Fracture: A Single-Centered Prospective Cohort Study.

BACKGROUND: Prognostic evaluation of elderly patients with hip fracture is an issue that has been highly concerned by clinicians. Only a few studies have focused on organ dysfunction after hip fracture in the elderly. This study aimed to investigate the association between high-sensitivity troponin T (hs-TnT) at admission and organ dysfunction during hospitalization in elderly patients with hip fracture. METHODS: We enrolled 168 patients with hip fracture who were aged 80 years and older at Geriatric Orthopaedic Center of Sichuan Provincial Orthopedic Hospital between January 2020 and August 2020. Baseline characteristics, perioperative information, and short-term clinical outcomes were analyzed. RESULTS: Of the 208 patients admitted during the study period, 168 met the inclusion criteria; of these, 91 (54.2%) had higher hs-TnT than the 99th percentile in the normal population. After adjustment for confounders, elevated hs-TnT was independently associated with multiple organ dysfunction syndrome in the elderly (MODSE) (adjusted OR, 5.76; 95% CI, 1.74-19.10; P = 0.004), heart dysfunction (adjusted OR, 7.48; 95% CI, 2.17-25.82; P = 0.001), MODS severity score > 3 (adjusted OR, 5.22; 95% CI, 1.32-20.60; P = 0.018), and length of hospital stay > 14 days (adjusted OR, 2.38; 95% CI, 1.05-5.36; P = 0.037). CONCLUSION: Increased hs-TnT on admission is an independent risk factor for MODSE after hip fracture in patients aged 80 years and older. Effective measures should be applied to avoid progression of MODSE from pre-failure stage to failure stage.

Adiponectin Treatment Attenuates Cerebral Ischemia-Reperfusion Injury through HIF-1α-Mediated Antioxidation in Mice.

Adiponectin (ADPN) plays an important role in cerebral ischemia-reperfusion injury. Although previous studies have confirmed that ADPN pretreatment has a protective effect on ischemic stroke, the therapeutic effect of ADPN on ischemic stroke and the underlying mechanism are still unclear. In order to clarify these questions, focal transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice and ADPN was administered for three times at 6 h, 24 h, and 48 h after reperfusion. Meanwhile, a virus-delivered HIF-1α siRNA was used before ADPN administration. The infarct volume, neurological score, cellular apoptosis, and oxidative stress were assessed at 72 h after reperfusion. The long-term outcome of mice after stroke was recorded as well. The results indicated that ADPN treatment reduced the infarct volume (P = 0.032), neurological deficits (P = 0.047), cellular apoptosis (P = 0.041), and oxidative responses (P = 0.031) at 72 h after MCAO. Moreover, ADPN increased both the protein level and transcriptional activity of HIF-1α as evidenced by the transcription levels of VEGF (P = 0.046) and EPO (P = 0.043) at 72 h after MCAO. However, knockdown of HIF-1α partially reversed the antioxidant and treatment effect of ADPN after cerebral ischemia. In the observation of long-term outcome after ADPN treatment, it demonstrated that ADPN not only prevented the cerebral atrophy (P = 0.031) and the neurological function decline (P = 0.048), but also promoted angiogenesis (P = 0.028) after stroke. In conclusion, our findings suggest that ADPN is effective in treatment of ischemic stroke which could be attributed to the increased antioxidant capacity regulated by HIF-1α.

2020 Chinese Expert-based Consensus on the Diagnosis and Treatment of Connective Tissue Disease Associated Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD) and is one of the leading causes of morbidity and mortality among patients with this condition. To establish an expert-based consensus on the diagnosis and treatment of CTD-associated PAH, a multidisciplinary consensus development panel was established. The consensus panel is composed of 45 experts in rheumatology, cardiology, pulmonology, and radiology, most of whom are members of the Group of Pulmonary Vascular and Interstitial Lung Diseases (ILD) Associated with Rheumatic Diseases. The consensus development panel compiled 9 recommendations for the diagnosis and treatment of CTD-associated PAH. It covers screening, diagnosis, disease evaluation, risk assessment, the use of immunosuppressive agents, and PAH-specific therapy with a treat-to-target approach. The consensus is intended to facilitate decision-making and standardize the care of CTD-associated PAH in China.

The Clinical and MRI Effect of TNF-α Inhibitors in Spondyloarthritis Patients With Hip Involvement: A Real-World Observational Clinical Study.

Objectives: Hip involvement is an important cause of disability and poor prognosis in patients with spondyloarthritis (SpA). Tumor necrosis factor (TNF)-α inhibitor treatment has been demonstrated to be effective in SpA patients with hip arthritis; however, quantitative assessment using MRI in long-term follow-up needs further application and observation. Methods: A total of 239 patients were involved in this study. Methotrexate and sulfasalazine were given as basic treatment. In total, 165 patients received TNF-α inhibitors plus basic treatment, and 74 received basic treatment only, as controls. Clinical symptoms were assessed at baseline and at weeks 12, 24, and 52. MRI performances of hip arthritis, including bone marrow edema (BME) and synovitis, were quantitatively assessed using the Hip Inflammation MRI Scoring System (HIMRISS). Results: The clinical values of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Harris hip score, and Ankylosing Spondylitis Disease Activity Score (ASDAS)-ESR in both groups showed significant clinical remission at week 52 (p < 0.001). However, the change in disease activity levels at week 52 in the control group was significantly worse than in the TNF-α inhibitor group. At week 52, MRI showed a significant remission trend in the TNF-α inhibitor group versus baseline, and total HIMRISS scores were significantly decreased (26.49 ± 10.37 vs. 20.59 ± 9.41, p < 0.001); the control group only had slight improvement (p < 0.05). Conclusions: TNF-α inhibitors could significantly improve clinical and MRI manifestations of hip involvement in patients with SpA. Quantitative MRI assessment combined with clinical assessment can be used to accurately evaluate the treatment effect of TNF-α in SpA patients with hip involvement to help guide targeted treatment.