• Biomarkers
• Cardiovascular complications
• Diagnostic markers
• Therapeutic targets
• circRNAs
• lncRNAs

• IVIG
• Kawasaki disease
• children
• paediatrics
• steroid
• steroid tapering
• vasculitis

• Humans
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Female
• Male
• Retrospective Studies
• Child, Preschool
• Immunoglobulins, Intravenous/therapeutic use
• Drug Therapy, Combination
• Infant
• Glucocorticoids/administration & dosage
• Treatment Outcome
• Recurrence
• Child
• Drug Administration Schedule
• Steroids/administration & dosage

• Kawasaki disease
• corticosteroid
• immunoglobulin
• pediatric
• vasculitis

• mortality
• systemic inflammatory response syndrome
• type A aortic dissection
• ulinastatin

• Humans
• Glycoproteins/therapeutic use
• Glycoproteins/pharmacology
• Aortic Dissection/surgery
• Aortic Dissection/drug therapy
• Male
• Female
• Middle Aged
• Systemic Inflammatory Response Syndrome/prevention & control
• Systemic Inflammatory Response Syndrome/drug therapy
• Systemic Inflammatory Response Syndrome/etiology
• Aged
• Multiple Organ Failure/prevention & control
• Inflammation/drug therapy
• Trypsin Inhibitors/therapeutic use

• biomarkers
• cardiology
• risk factors

• Humans
• Mucocutaneous Lymph Node Syndrome/blood
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Immunoglobulins, Intravenous/therapeutic use
• Male
• Female
• Neutrophils
• Child, Preschool
• Drug Resistance
• Infant
• Biomarkers/blood
• Retrospective Studies
• Child
• Albumins/metabolism

• 2022YFS0627 Sichuan Science and Technology Program
• 2023LZXNYDJ042 Luzhou Municipal People's Government-Southwest Medical University Science and Technology strategic cooperation

• Kawasaki disease
• apheresis
• child
• infant
• therapeutic plasma exchange

• Humans
• Mucocutaneous Lymph Node Syndrome/therapy
• Plasma Exchange/methods
• Male
• Female
• Retrospective Studies
• Child, Preschool
• Infant
• Body Weight
• Child
• Treatment Outcome
• C-Reactive Protein/metabolism

• Antiphospholipid syndrome
• Autoimmunity
• Guillain-Barré syndrome
• Kawasaki disease
• Long COVID

• BCL2L1
• Bioinformatics analysis; Hub genes
• ITGAM
• Kawasaki disease
• Neutrophils

• Humans
• Gene Expression Profiling/methods
• Mucocutaneous Lymph Node Syndrome/genetics
• Neutrophils/metabolism
• Reproducibility of Results
• Computational Biology/methods
• RNA, Messenger/genetics
• Sphingolipids
• Gene Regulatory Networks
• ATPases Associated with Diverse Cellular Activities/genetics
• ATPases Associated with Diverse Cellular Activities/metabolism
• Carrier Proteins/genetics
• DNA Helicases/genetics
• DNA Helicases/metabolism

• 81700439 National Natural Science Foundation of China
• 82000467 National Natural Science Foundation of China
• GSWS2022059 Gusu health personnel training project

• Child, Preschool
• Humans
• Infant
• Acute Disease
• Immunoglobulins, Intravenous/therapeutic use
• Japan
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Plasma Exchange
• Practice Guidelines as Topic

Kawasaki disease (KD), first reported as an acute febrile mucocutaneous lymph node syndrome, is a self-limiting vasculitis of unknown etiology. The most important aspect of KD is the prevention of coronary artery lesion (CAL) because myocardial ischemia or infarction due to CAL might be lethal. In addition to the CAL, patients with KD develop systemic vasculitis, which indicates the presence of vascular endothelial damage. Studies assessing pulse wave velocity or percentage change in flow-mediated dilatation have shown that aortic stiffness is increased in patients with KD history. In contrast, the cardio-ankle vascular index, a novel parameter not affected by blood pressure, has not demonstrated increased aortic stiffness in patients with KD. Although many studies using various parameters have suggested a risk of atherosclerosis in patients with a history of KD, a few others have reported no significant differences between KD patients and controls. Therefore, it will be necessary to thoroughly understand the characteristics of each parameter, before evaluating the results of those studies, to understand systemic vascular dysfunction in these populations, and to manage their vascular health. Although it is controversial whether the risk of atherosclerosis in patients with KD is higher, those with CAL are thought to be at a high risk of atherosclerosis. Therefore, appropriate treatment to prevent CAL in the acute phase and subsequent regular follow-up is important. Here, we review the pathology, risk, and management of vascular disorders, especially systemic vascular disorders, in patients with KD history.

• aortic stiffness
• atherosclerosis
• vascular health
• vasculitis

Acute type A aortic dissection (ATAAD) is a heterogeneous systemic inflammatory response syndrome. Identification of distinct inflammatory phenotypes may allow more precise therapy and improved care. We aim to investigate whether distinct inflammatory subphenotypes exist in ATAAD patients and respond differently to pharmacotherapies.

Retrospective analysis of data sets was conducted from the Additive Anti-inflammatory Actions for Aortopathy & Arteriopathy (5A) III study. Inflammatory subphenotypes were derived among 2008 ATAAD patients who received surgical repair at 11 Chinese hospitals (2016–2020) using latent class analysis applied to 14 laboratory signatures within 6 hours of hospital admission. Outcomes included operative mortality (Society of Thoracic Surgeons definition), derived subphenotype frequency, and the potential consequences of phenotype frequency distributions on the treatment effects.

The median (interquartile range) age of patients was 54 (45–62) years, and 1423 (70.9%) were male. A two-class (two subphenotype) model was an improvement over a one-class model (P<·001), with 1451 (72.3%) patients in the hypoinflammatory subphenotype group and 557 (27.7%) in the hyperinflammatory subphenotype group. Patients with the hyperinflammatory subphenotype had higher operative mortality (71 [12.7%] vs 127 [8.8%]; P=0·007) than did those with the hypoinflammatory subphenotype. Furthermore, the interaction between ulinastatin treatment and subphenotype is not significant for operative mortality (P=0.15) but for ventilator time (P=0·04).

Two subphenotypes of ATAAD were identified in the 5A cohort that correlated with clinical outcomes, with significant interaction effect between anti-inflammatory treatment and subphenotypes for ventilator time, suggesting these phenotypes may help in understanding heterogeneity of treatment effects.

Clinical Trials. Gov: number NCT04918108.

• National Natural Science Foundation of China
• Common Program of Beijing Municipal Commission of Education
• Beijing Municipal Science and Technology Commission

• IVIG non-responsiveness
• Kawasaki disease
• children
• coronary artery lesions
• tenascin-C

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid-19). The present study aimed to assess the efficacy of high-dose ulinastatin for the treatment of patients with Covid-19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid-19 and two patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48-87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high-dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid-19.

• coronavirus disease 2019
• cytokine storm
• inflammation
• protease inhibitor
• ulinastatin

• Kawasaki disease
• aneurysm
• coronary artery disease
• cyclosporine A
• vasculitis

• Candida albicans
• Kawasaki disease
• coronary aneurysm
• sivelestat
• vasculitis

• Angiography
• Cardiac
• Coronary Arteries
• Pediatrics

• Burns
• capillaries
• endothelium
• permeability

The causation of Kawasaki disease has been a medical mystery for over 54 years. However, the causations of Kawasaki disease, its variations, and COVID-19-associated Multisystem Inflammatory Syndrome have been recently explained to involve high replication rate viral infections. In a subset of patients, the extensive antigen-antibody immune complexes that are not quickly cleared by phagocytosis will create a type III hypersensitivity immune reaction. The subsequent release of proteases and other enzymes and the expression or exposure of new immunogenic antigens due to protease attacks on basement membranes of epithelial cells or endothelial cells in blood vessels will induce new autoantibodies and cause Kawasaki disease, its variations, and COVID-19-related Multisystem Inflammatory Syndrome. There is now increasing evidence that a viral infection of a large surface area of tissue, such as the respiratory tract, gastrointestinal tract or blood vessels, and a resultant type III hypersensitivity immune reaction is the most plausible explanation for the causations of Kawasaki disease, its variations, and COVID-19-related Multisystem Inflammatory Syndrome. Furthermore, an improved understanding of these causations also suggests several potential new treatments which can be more effective.

• Hypersensitivity reactions;
• Inflammation
• Kawasaki disease;
• Multisystem Inflammatory Syndrome;
• Respiratory infections;
• Virus infections;

• Coronary artery endothelial cells
• Corticosteroid
• G-CSF
• HMGB1
• IL-1α
• IL-6
• IVIG
• IgG
• Kawasaki disease

• TSG-6
• bikunin
• chondroitin sulfate
• extracellular matrix
• glycosaminoglycan
• heavy chain
• inter-α inhibitor proteins
• inter-α-trypsin inhibitor
• proteoglycan

• Intravenous immunoglobulin resistance
• Kawasaki disease
• Neutrophil-to-lymphocyte ratio
• Platelet-to-lymphocyte ratio
• White blood cell

• biomarker
• kawasaki disease
• meta-analysis
• neutrophil-to-lymphocyte ratio

• Biomarkers/blood
• Drug Resistance
• Humans
• Immunoglobulins, Intravenous/therapeutic use
• Lymphocytes/cytology
• Mucocutaneous Lymph Node Syndrome/blood
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Neutrophils/cytology

• Diagnosis Procedure Combination inpatient database
• Kawasaki disease
• clinical guideline
• coronary artery aneurysm
• healthcare utilization
• practice pattern

• Infliximab
• Intravenous immunoglobulin
• Intravenous methylprednisolone pulse
• Kawasaki disease
• Prednisolone

• Kawasaki disease
• coronary artery lesion
• i.v. immunoglobulin
• neutrophil elastase
• sivelestat sodium hydrate

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective loss of dopamine neurons in the substantia nigra pars compacta of the midbrain. Reports from postmortem studies in the human PD brain, and experimental PD models reveal that endoplasmic reticulum (ER) stress is implicated in the pathogenesis of PD. In times of stress, the unfolded or misfolded proteins overload the folding capacity of the ER to induce a condition generally known as ER stress. During ER stress, cells activate the unfolded protein response (UPR) to handle increasing amounts of abnormal proteins, and recent evidence has demonstrated the activation of the ER chaperone GRP78/BiP (78 kDa glucose-regulated protein/binding immunoglobulin protein), which is important for proper folding of newly synthesized and partly folded proteins to maintain protein homeostasis. Although the activation of this protein is essential for the initiation of the UPR in PD, there are inconsistent reports on its expression in various PD models. Consequently, this review article aims to summarize current knowledge on neuroprotective agents targeting the expression of GRP78/BiP in the regulation of ER stress in experimental PD models.

• Burn
• Hypovolemic shock
• Organ function
• Ulinastatin
• Vasopermeability

• Animals
• Burns/complications
• Burns/physiopathology
• Capillary Permeability/drug effects
• Dogs
• Female
• Fluid Therapy
• Glycoproteins/pharmacology
• Hemodynamics/drug effects
• Male
• Random Allocation
• Serine Proteinase Inhibitors/pharmacology
• Shock/etiology
• Shock/therapy

• Immune response
• Inflammation
• Regulatory T cell (Treg)
• Sepsis
• TLR4
• Ulinastatin

• Aspirin
• Child
• Coronary artery abnormalities
• Innovative biotechnologies
• Intravenous immunoglobulin
• Kawasaki disease
• Personalized medicine

• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Cardiovascular Diseases/diagnosis
• Cardiovascular Diseases/drug therapy
• Cardiovascular Diseases/epidemiology
• Child
• Child, Preschool
• Coronary Artery Disease/diagnosis
• Coronary Artery Disease/drug therapy
• Coronary Artery Disease/epidemiology
• Drug Resistance
• Female
• Follow-Up Studies
• Humans
• Immunoglobulins, Intravenous/therapeutic use
• Male
• Mucocutaneous Lymph Node Syndrome/diagnosis
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Mucocutaneous Lymph Node Syndrome/epidemiology
• Pediatrics
• Practice Guidelines as Topic
• Risk Assessment
• Severity of Illness Index
• Societies, Medical

• coronary artery aneurysms
• initial therapy
• intravenous immunoglobulin
• methylprednisolone pulse

Pulmonary fibrosis is a chronic, progressive, lethal lung disease characterized by alveolar cell necrosis and dysplasia of interstitial fibrotic tissue, resulting in loss of lung function and eventual respiratory failure. Previously, glucocorticoid drugs were used to treat this lung disorder. However, positive responses were recorded in less than half of treated patients and the cytotoxicity caused by high dosage treatment is still a concern. The present study investigated whether ulinastatin, a typical urinary trypsin inhibitor that mitigates numerous inflammatory responses, could be a treatment option for lung fibrosis. The results demonstrated that ulinastatin had the ability to ameliorate interstitial fibrosis and alveolar exudates and to protect against lung diseases induced by smoke, irradiation or silica particles. The mechanism of ulinastatin resulted in the downregulation of inflammatory cascades: Transforming growth factor-β1, tumor necrosis factor-α and nuclear factor-κB, as demonstrated by western blotting and ELISA. Ulinastatin treatment with a high dose (100,000 U/kg body weight/day) resulted in an attenuated inflammatory response, and inhibited fibrosis formation in lungs, suggesting that ulinastatin may become a part of a clinical therapeutic strategy.

• Meta-analysis
• Sepsis
• Ulinastatin

• Adult
• China
• Glycoproteins/therapeutic use
• Humans
• India
• Inflammation
• Intensive Care Units
• Interleukin-10/metabolism
• Interleukin-6/metabolism
• Length of Stay
• Middle Aged
• Randomized Controlled Trials as Topic
• Research Design
• Respiration, Artificial
• Sepsis/drug therapy
• Sepsis/mortality
• Severity of Illness Index
• Software
• Survival Rate
• Thymalfasin
• Thymosin/analogs & derivatives
• Thymosin/therapeutic use
• Treatment Outcome
• Tumor Necrosis Factor-alpha/metabolism

• Blood Cell Count/methods
• Blood Platelets
• Drug Resistance
• Female
• Humans
• Immunoglobulins, Intravenous/therapeutic use
• Immunologic Factors/therapeutic use
• Infant
• Lymphocytes
• Male
• Mucocutaneous Lymph Node Syndrome/blood
• Mucocutaneous Lymph Node Syndrome/diagnosis
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Neutrophils
• Odds Ratio
• Prognosis
• Retrospective Studies
• Risk Assessment
• Sensitivity and Specificity
• Treatment Outcome

• Japan Kawasaki Disease Research center
• Kawasaki Disease Research from Japan Blood Products Organization
• Grant-in-Aid for Scientific Research (KAKENHI)

• Biomarkers/metabolism
• Biomarkers, Pharmacological/metabolism
• Cardiovascular Diseases/diagnosis
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/therapy
• Cell Count
• Humans
• Immunoglobulins, Intravenous/therapeutic use
• Mucocutaneous Lymph Node Syndrome/diagnosis
• Mucocutaneous Lymph Node Syndrome/epidemiology
• Mucocutaneous Lymph Node Syndrome/therapy
• Neutrophils/pathology
• Prognosis
• Risk

Abnormal urinary findings, such as sterile pyuria, proteinuria, and microscopic hematuria, are often seen in the acute phase of Kawasaki disease (KD). We investigated the potential significance of urinary lactate dehydrogenase (U-LDH) activity and its isozyme patterns in KD. Total U-LDH activity and its isozymes (U-LDH1-5) levels were compared among 120 patients with KD, 18 patients with viral infection (VI), and 43 patients with upper urinary tract infection (UTI) and additionally compared between intravenous immunoglobulin (IVIG) responders (n = 89) and nonresponders (n = 31) with KD. Total U-LDH activity was higher in KD (35.4 ± 4.8 IU/L, P < 0.05) and UTI patients (66.0 ± 8.0 IU/L, P < 0.01) than in VI patients (17.0 ± 6.2 IU/L). In the isozyme pattern analysis, KD patients had high levels of U-LDH1 and U-LDH2, while UTI patients had high levels of U-LDH3, U-LDH4, and U-LDH5. Furthermore, IVIG nonresponders of KD had significantly higher levels of total U-LDH activity (45.1 ± 4.7 IU/L, P < 0.05), especially U-LDH1 and U-LDH2 (P < 0.05), than IVIG responders (32.0 ± 2.8 IU/L). KD patients have increased levels of total U-LDH activity, especially U-LDH-1 and U-LDH2, indicating a unique pattern of U-LDH isozymes different from that in UTI patients.

Resistance to intravenous immunoglobulin (IVIG) occurs in 10–20% of patients with Kawasaki disease (KD). The risk of resistance is about two-fold higher in patients with elevated gamma glutamyl transferase (GGT) levels. We sought to understand the biological mechanisms underlying IVIG resistance in patients with elevated GGT levels.

We explored the association between elevated GGT levels and IVIG-resistance with a cohort of 686 KD patients (Cohort I). Gene expression data from 130 children with acute KD (Cohort II) were analyzed using the R square statistic and false discovery analysis to identify genes that were differentially represented in patients with elevated GGT levels with regard to IVIG responsiveness. Two additional KD cohorts (Cohort III and IV) were used to test the hypothesis that sialylation and GGT may be involved in IVIG resistance through neutrophil apoptosis.

Thirty-six genes were identified that significantly explained the variations of both GGT levels and IVIG responsiveness in KD patients. After Bonferroni correction, significant associations with IVIG resistance persisted for 12 out of 36 genes among patients with elevated GGT levels and none among patients with normal GGT levels. With the discovery of ST6GALNAC3, a sialyltransferase, as the most differentially expressed gene, we hypothesized that sialylation and GGT are involved in IVIG resistance through neutrophil apoptosis. We then confirmed that in Cohort III and IV there was significantly less reduction in neutrophil count in IVIG non-responders.

Gene expression analyses combining molecular and clinical datasets support the hypotheses that: (1) neutrophil apoptosis induced by IVIG may be a mechanism of action of IVIG in KD; (2) changes in sialylation and GGT level in KD patients may contribute synergistically to IVIG resistance through blocking IVIG-induced neutrophil apoptosis. These findings have implications for understanding the mechanism of action in IVIG resistance, and possibly for development of novel therapeutics.

• coronary artery abnormality
• white blood cell

• aneurysm
• coronary aneurysm
• coronary thrombosis
• immunoglobulin
• intravenous
• mucocutaneous lymph node syndrome
• myocardial infarction

• Coronary artery lesion
• High-dose intravenous immunoglobulin
• Kawasaki disease
• Mucocutaneous lymph node syndrome
• Pseudo-Pelger‐Huët anomaly

Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.

Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.

The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.

HLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.

• Acetylglucosaminidase/urine
• Acute Kidney Injury/drug therapy
• Acute Kidney Injury/prevention & control
• Animals
• Anti-Inflammatory Agents/therapeutic use
• Biomarkers/blood
• Biomarkers/urine
• Cardiac Surgical Procedures/adverse effects
• Cardiopulmonary Bypass/adverse effects
• Glycoproteins/therapeutic use
• In Situ Nick-End Labeling
• Interleukin-6/blood
• Kidney/cytology
• Kidney/physiopathology
• Models, Animal
• Oxidative Stress/physiology
• Reperfusion Injury/pathology
• Swine
• Systemic Inflammatory Response Syndrome/pathology
• Thoracotomy/adverse effects
• Tumor Necrosis Factor-alpha/blood

• CLINICAL PHARMACOLOGY

• Aspirin/therapeutic use
• Calcineurin Inhibitors/administration & dosage
• Calcineurin Inhibitors/adverse effects
• Child, Preschool
• Cyclosporine/administration & dosage
• Cyclosporine/adverse effects
• Drug Therapy, Combination
• Female
• Humans
• Immunoglobulins, Intravenous/administration & dosage
• Immunoglobulins, Intravenous/adverse effects
• Infant
• Japan
• Male
• Mucocutaneous Lymph Node Syndrome/drug therapy
• Proportional Hazards Models
• Research Design
• Treatment Outcome