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Residues of herbicides with the extensive applications may impact the soil ecosystem and ultimately threaten agricultural sustainability. However, the effects of long-term herbicide residues on soil multifunctionality and the soil microbial community remain poorly understood. Here, we evaluated relationships between soil multifunctionality and soil microbial communities with residual herbicide concentrations by surveying and analyzing 62 black soil samples collected from an agricultural area in northeastern China. Total residual herbicide concentrations varied from 35 to 568⯵g/kg in the soil samples. The response of soil multifunctionality to increasing residual herbicide concentrations exhibited an inverted U-shaped relationship with a peak at approximately 310⯵g/kg, with net mineralized organic nitrogen (Nm) and total nitrogen (TN) exhibiting the same trend. Microbial community richness was significantly lower in soil samples with high residual herbicide concentrations (> 310⯵g/kg, HG) compared to low residual herbicide concentrations (< 310⯵g/kg, LG). In addition, the relative abundances of specific keystone microbial genera differed significantly between LG and HG: norank_f_Acetobacteraceae, norank_f_Caldilineaceae, Candidatus_Alysiosphaera, and Gonytrichum. The relative abundances of these genera were also significantly correlated with soil multifunctionality. Structural equation models (SEMs) further showed that herbicide residues influenced soil multifunctionality by affecting these specific keystone genera. Our study demonstrates that long-term herbicide residues significantly impact the multifunctionality of agricultural black soil, where low concentrations stimulate while high concentrations inhibit, underscoring the need for reasonable application of herbicides to maintain soil ecosystem health.
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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.
Subject(s)
Environmental Monitoring , Groundwater , Herbicides , Water Pollutants, Chemical , China , Risk Assessment , Herbicides/analysis , Herbicides/toxicity , Water Pollutants, Chemical/analysis , Groundwater/chemistry , CitiesABSTRACT
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.
Subject(s)
Basigin , Immunological Synapses , Lymphocyte Activation , T-Lymphocytes , Basigin/metabolism , Basigin/immunology , Immunological Synapses/metabolism , Immunological Synapses/immunology , Lymphocyte Activation/immunology , Humans , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Signal Transduction/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Phosphorylation , Antibodies, Monoclonal/immunology , Macrophages/immunology , Macrophages/metabolism , B-Lymphocytes/immunology , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Interleukin-2/metabolism , Interleukin-2/immunology , Animals , Jurkat CellsABSTRACT
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.
Subject(s)
Machine Learning , Scleroderma, Systemic , Scleroderma, Systemic/mortality , Humans , Female , Middle Aged , Male , Prognosis , Adult , Risk Factors , Proportional Hazards Models , Nomograms , China/epidemiology , Survival Analysis , AgedABSTRACT
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.
Subject(s)
Spondylarthritis , Spondylitis, Ankylosing , Humans , HLA-B27 Antigen , Spondylarthritis/diagnosis , Spondylarthritis/therapy , Severity of Illness Index , PatientsABSTRACT
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.
Subject(s)
Arthritis, Juvenile , Joint Diseases , Male , Humans , Child , Joint Diseases/diagnosis , MutationABSTRACT
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.
Subject(s)
Gardenia , Lipopolysaccharides , Swine , Animals , NF-kappa B/metabolism , Network Pharmacology , Iridoids/pharmacology , Iridoids/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
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.
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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.
Subject(s)
COVID-19 , Humans , Adult , SARS-CoV-2 , Interleukin-8 , CytokinesABSTRACT
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.
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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).
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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.
Subject(s)
Deep Learning , Spondylitis, Ankylosing , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Edema/diagnostic imaging , Edema/etiology , Humans , Magnetic Resonance Imaging/methods , Retrospective Studies , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/pathologyABSTRACT
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.
Subject(s)
Adalimumab/therapeutic use , Etanercept/therapeutic use , Hip/pathology , Infliximab/therapeutic use , Spondylitis, Ankylosing/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab/pharmacology , Adolescent , Adult , Etanercept/pharmacology , Female , Hip/diagnostic imaging , Humans , Infliximab/pharmacology , Magnetic Resonance Imaging , Male , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
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.
Subject(s)
Adiponectin/therapeutic use , Antioxidants/therapeutic use , Brain Ischemia/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Reperfusion Injury/drug therapy , Adiponectin/pharmacology , Animals , Antioxidants/pharmacology , Disease Models, Animal , Male , Mice , TransfectionABSTRACT
Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 Drug Treatment , COVID-19/metabolism , Lung/metabolism , SARS-CoV-2/metabolism , Adolescent , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/pharmacokinetics , COVID-19/pathology , Double-Blind Method , Female , Humans , Lung/pathology , Lung/virology , Male , Middle AgedABSTRACT
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.
Subject(s)
Hip Fractures/complications , Hospitalization/statistics & numerical data , Multiple Organ Failure/etiology , Troponin T/blood , Aged, 80 and over , Biomarkers , Female , Heart Diseases/epidemiology , Humans , Length of Stay , Male , Multiple Organ Failure/epidemiology , Prognosis , Prospective Studies , Risk Factors , Severity of Illness IndexABSTRACT
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.
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OBJECTIVE: To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren's syndrome (pSS). METHODS: Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher's exact analysis, Mann-Whitney U-test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value. RESULTS: Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%). CONCLUSION: This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.
Subject(s)
Biomarkers , Epithelial Cell Adhesion Molecule/genetics , Epithelial Cell Adhesion Molecule/metabolism , Sjogren's Syndrome/etiology , Sjogren's Syndrome/metabolism , Adolescent , Adult , Cell Nucleus/metabolism , Cytoplasm/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Prognosis , ROC Curve , Risk Factors , Sensitivity and Specificity , Sjogren's Syndrome/diagnosis , Young AdultABSTRACT
Gardenia jasminoides Ellis, which belongs to the Rubiaceae family, is a widely used traditional Chinese medicine. Although effect of Gardenia jasminoides Ellis has been widely reported, its anti-inflammatory role in intestinal mucosal injury induced by LPS remains unclear. In the present study, we investigated the effects of decoction extracted from Gardenia jasminoides on the morphology and intestinal antioxidant capacity of duodenum induced by LPS in mice. Further analysis was carried out in the expression of inflammatory and anti-inflammatory cytokines. Nuclear factor-kappa B (NF-κB) was determined by Western blot. Gardenia jasminoides water extract was qualitative analyzed by high-performance liquid chromatography coupled with electro spray ionization quadrupole time-of-flight mass spectrometry. The results showed that Gardenia decoction markedly inhibited the LPS-induced Tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-8, and IL-1 production. It was also observed that Gardenia decoction attenuated duodenum histopathology changes in the mouse models. Furthermore, Gardenia decoction inhibited the expression of NF-κB in LPS stimulated mouse duodenum. These results suggest that Gardenia decoction exerts an anti-inflammatory and antioxidant property by up-regulating the activities of the total antioxidant capacity (T-AOC), the total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px). Gardenia decoction is highly effective in inhibiting intestinal mucosal damage and may be a promising potential therapeutic reagent for intestinal mucosal damage treatment.
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AIMS: Spondyloarthritis (SpA) is an inflammatory rheumatic disease and hip involvement often results in severe deformities and functional impairment. Magnetic resonance imaging (MRI) is a powerful imaging tool for detecting early hip lesions in SpA. The aims of this study are to apply the hip inflammation MRI scoring system (HIMRISS) in SpA patients and to evaluate its reproducibility and validity. METHODS: Four readers new to HIMRISS (two radiologists and two rheumatologists) scored the MRI scans obtained from a total of 55 SpA patients with hip lesions in two separate exercises (33 patients in exercise 1 and 22 patients in exercise 2). After the training and review process for exercise 1, these well-trained readers with expertise in the HIMRISS method scored the scans obtained from 22 patients and evaluated the association between HIMRISS and clinical activity of SpA, including Ankylosing Spondylitis Disease Activity Score (ASDAS), laboratory features, Bath Ankylosing Spondylitis Disease Activity Index and Harris hip scores. RESULTS: HIMRISS is a reliable MRI scoring method for bone merrow lesions (BML) and synovitis in SpA. After 2 training exercises, the reliability improved from 0.67 to 0.90. The reliability for detecting femoral BML, acetabular BML, and synovitis effusion was very good after the 2 exercises (overall intraclass correlation coefficient = 0.73, 0.84 and 0.88, respectively). The clinical correlations between HIMRISS and ASDAS were most significant, and the correlations were closer to summed bilateral HIMRISS scores than just the worse side. HIMRISS was found to be an excellent tool for the early diagnosis of inflammation before the occurrence of structural damage, which was not significantly reflected in the systemic diagnosis. CONCLUSION: HIMRISS offers a reliable MRI scoring method for hip joint in SpA, and it is beneficial for early detection and fast quantification in disease activity assessment.