Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Stress-related digestive tract mucosal disease is a common complication in pediatric intensive care unit(PICU). It may progress to stress ulcer and severe ulcer bleeding, which may lead to death.Currently, stress ulcer prophylaxis is recommended for critically ill children with high risk factors for stress ulcer, and the most commonly used acid suppression drugs are proton pump inhibitor and histamine-2 receptor antagonist.However, excessive prophylactic acid suppression is common and can increase the risk of hospital-acquired pneumonia and clostridium difficile infection in PICU.This review aimed to analyze the advantages and disadvantages of preventive acid suppressant therapy and promote the rational use of acid suppressant in PICU.

Arrhythmia-induced cardiomyopathy(AIC) is an reversible dilated cardiomyopathy and appears to occur at any age.The morbidity of AIC is unclear and likely underestimated.The pathophysiology and mechanism of AIC is unknown.It is often difficult to determine whether arrhythmias are the cause or result of cardiac dysfunction.The diagnosis of AIC can be only confirmed after recovery or improvement of cardiac function after elimination of the tachyarrhythmia.Tachycardias, ventricular premature contraction, left bundle branch block and ventricular preexcitation are known to trigger AIC.Appropriate diagnosis and treatment of AIC can reverse cardiac function.However, arrhythmia recurrence can lead to rapid recurrence of AIC and symptoms of heart failure.

Objective:To analyze the characteristics of coronary artery lesions in infants under 6 months of age with Kawasaki disease(KD), and to explore their regression and risk factors.Methods:The clinical data of 61 infants with KD[34 boys, 24 girls, aged 2.2 (1.7, 3.1) months] admitted to the department of critical care medicine and neonatology, Children′s Hospital, Capital Institute of Pediatrics from October 2015 to February 2020 were retrospectively analyzed.Persistent coronary artery aneurysm(CAA)was defined as the persistent enlargement of coronary arteries(coronary Z-score≥2.5)on echocardiograms at 12 months after KD onset.Cox proportional hazards mode was conducted to evaluate the potential risk factors of persistent CAA.Results:The incidence of CAA in 61 infants with KD was 52.5% (32/61) and occurred on 5 (4, 8)d of the disease course.During a follow-up of 547 (399, 782)d, five(8.2%, 5/61)infants satisfied the definition of persistent CAA.The median recovery time of CAA was 20 (12, 82)d after KD onset.Cox proportional hazards mode revealed that the maximal coronary Z-score was an independent factor of CAA regression( HR=0.451, 95% CI 0.293-0.694, P<0.001). Receiver operating characteristic curve analysis showed that the best cutoff value of coronary Z-score for predicting persistent CAA was 6.15(sensitivity 80.0%, specificity 97.7%). Conclusion:CAA is common in infants younger than 6 months with KD.The maximal coronary Z-score is an independent factor of persistent CAA.

Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.

Objective:To investigate the clinical features and risk factors of left ventricular systolic dysfunction in children with septic shock.Methods:A retrospective analysis was performed on the clinical data of children diagnosed with septic shock in the Department of Critical Care Medicine of Children’s Hospital, Capital Institute of Pediatrics from February 2016 to June 2021. Inclusion criteria: (1) patients met the diagnostic criteria of septic shock; (2) Cardiac ultrasound was performed within 48 h after shock treatment and was dynamically monitored during shock treatment. Exclusion criteria: (1) Previous history of chronic cardiac insufficiency, cardiomyopathy, or organic heart disease; (2) patients with acute cerebral infarction, cerebral hemorrhage and necrotizing encephalopathy; (3) congenital genetic metabolic diseases; and (4) incomplete information. Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction (LVEF) <50% and a ≥10% decrease in the patient’s initial LVEF assessed on admission. Patients with left ventricular systolic dysfunction and without left ventricular systolic dysfunction were compared. Comparisons between groups were performed with unpaired Student’s t test, or Mann-Whitney U test, or chi-square test. Multivariate logistic regression analysis was used to analyze the correlation factors of left ventricular systolic dysfunction. Results:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0% with the lowest LVEF of (42±8)%. Left ventricular systolic dysfunction occurred on (2.4±1.3) days after shock onset, and the LVEF returned to normal on (6.7±3.3) days. Hematogenous infection was more frequent (77.8% vs. 40.5%, P=0.018), ventilator application (83.3% vs. 50.0%, P=0.033) and inotropes and vasopressor drugs (100.0% vs. 64.3%, P=0.009) were used more frequently in patients with left ventricular systolic dysfunction(n =18), compared with patients without left ventricular systolic dysfunction(n =42). Patients with left ventricular systolic dysfunction had a lower LVEF [(42±8)% vs. (67±5)%, P<0.001], a lower pediatric critical illness score [(64±13) vs. (76±14), P=0.003], a lower resuscitation success rate at 6 h (38.9% vs. 73.8%, P=0.010), a higher lactate at admission [3.80 (3.15, 5.88) mmol/L vs. 2.70 (1.85, 3.80) mmol/L, P=0.001) and a higher 28-d mortality (38.9% vs. 12.8%, P=0.025) compared with patients without left ventricular systolic dysfunction. Hematogenic infection ( OR=7.358, 95% CI: 1.198~45.197, P=0.031) and lactate at admission ( OR=1.743, 95% CI: 1.041~2.917, P=0.034) were independent risk factors for left ventricular systolic dysfunction. Conclusions:The incidence of left ventricular systolic dysfunction in children with septic shock was 30.0%. Left ventricular systolic dysfunction usually occurred on (2.4±1.3) days after shock onset and resolved within 7 days, which was associated with 28-d mortality. Hematogenous infection and high lactate value were independent risk factors for left ventricular systolic dysfunction.

Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Objective:To estimate the predictive value of heart rate (HR)-blood pressure (BP) products of multiplication for compensated shock in children.Methods:The study population consisted of 99 children with shock who had lactate measured before receiving vasopressor agents in Department of Critical Care Medicine of Children′s Hospital, Capital Institute of Pediatrics from October 2015 to March 2021. The clinical data including the HR, BP, HR to BP ratio, HR-BP product and lactate at admission and after the correction of shock, as well as the 28-day mortality were collected. According to the outcome at the 28 th day, the patients were divided into survival group and non-survival group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test. Pearson correlation analysis was used to analyze the correlations between lactate and HR, BP, HR to BP ratio and HR-BP product, respectively. Receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive values of HR, BP, HR to BP ratio and HR-BP product for lactate greater than 2 mmol/L. Results:In these 99 children, 49 were males, and the median age was 3.8 (0.7-6.0) years. The most common type of shock was septic shock (61 cases, 62%), followed by cardiogenic shock (12 cases, 12%), hemorrhagic shock (12 cases, 12%), Kawasaki disease shock syndrome (8 cases, 8%) and anaphylactic shock (6 cases, 6%). Sixty-six patients (67%) survived, and 33 patients (33%) died. ROC curve showed that the area under curves (AUC) of lactate (optimal cutoff value 3.15 mmol/L, sensitivity 96.0%, specificity 54.4%, P<0.01) and HR to systolic blood pressure ratio (HR/SBP) (optimal cutoff value 2.0 times/(min·mmHg), sensitivity 62.5%, specificity 69.0%, P = 0.03) for predicting adverse outcome were 0.769 and 0.649, respectively. There were significant correlations between lactate and HR to diastolic blood pressure (DBP) ratio, HR to mean blood pressure (MBP) ratio, SBP, HR/SBP, MBP, DBP and HR ( r= 0.476, 0.452, -0.444, 0.425,-0.410, -0.364, 0.177, all P<0.01), while no significant correlation was found between lactate and the products of HR and BP(all P>0.05). HR/SBP performed better than the other six parameters for predicting lactate>2 mmol/L, with the AUC of 0.872 and the optimal cutoff value of 1.4 bpm/mmHg (sensitivity 92.1%, specificity 70.9%, P<0.01). When MBP was greater than or equal to 65 mmHg, MBP × HR, DBP × HR, SBP × HR, HR, HR/SBP, HR/MBP and HR/DBP were significantly correlated with lactate ( r= 0.706, 0.705, 0.669, 0.626, 0.555, 0.502, 0.446, all P<0.01). And MBP × HR performed better for predicting lactate>2 mmol/L than the other six parameters, with the AUC of 0.974 and the optimal cutoff value of 9446 bpm × mmHg (sensitivity 100.0%, specificity 90.9%, P<0.01). Conclusions:The product of HR and BP, especially the MBP × HR, shows higher predictive values for abnormally elevated lactate in children with compensated shock than the HR/SBP does. It is worth recommending for early identification of compensated shock in children.