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.

Objective:To investigate the changes in thyroid hormone levels and inflammatory markers in critically ill children，analyze their correlation with disease severity，and explore their potential impact on prognosis,providing references for clinical management and prognosis assessment in critical illness.Methods:A retrospective cohort study was conducted involving 394 pediatric patients admitted to the ICU of the Capital Pediatric Institute Affiliated Children's Hospital from 2019 to 2023.Based on the pediatric critical illness score,patients were divided into three groups:the extremely critical group (score ≤ 70, n=81),the critical group (score 71–80, n=150),and the non-critical group (score>80, n=163).Data collected included thyroid function indicators，inflammatory markers[C-reactive protein（CRP)，procalcitonin(PCT),tumor necrosis factor(TNF)-α，interleukin (IL)，etc.]，clinical information，and outcomes.The correlation between thyroid function indicators and inflammatory markers were analyzed.The predictive value of thyroid function indicators and inflammatory markers for prognosis in critically ill pediatric patients was assessed. Results:Of the 394 children,non-thyroidal disease syndrome occurred in 321 cases,with an overall incidence of 81.5%,which increased with disease severity.Thyroid hormone [total triiodothyronine (TT3),free triiodothyronine (FT3),and total tetraiodothyronine (TT4)] levels were significantly lower in the extremely critical group than in the other groups ( P<0.05).Inflammatory markers such as CRP,PCT,TNF-α,IL-6,IL-8,and IL-10 were significantly higher in the extremely critical group than in the other groups ( P<0.05).Thyroid hormones were negatively correlated with inflammatory markers,and the receivor operating characteristic curves analysis indicated that TT3,FT3,IL-6 and IL-8 levels,could effectively differentiate disease prognosis.Univariate regression model showed significant associations between TT3,FT3,TT4,PCT,IL-8,and IL-10 and disease prognosis.The multivariate Logistic regression model showed IL-6 and IL-8 were independent predictors of disease prognosis. Conclusion:Significant reductions in thyroid hormone levels are closely related to disease severity and poor prognosis.Changes in inflammatory markers reflect the inflammatory state and severity of the disease and impact prognosis.Monitoring thyroid function and inflammatory status is important in clinical management，which provids new insights into prognosis assessment and treatment strategies for critically ill children.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Acquired severe aplastic anemia (SAA) in children is a bone marrow failure disease characterized by reduced proliferation of marrow nucleated cells and decreased peripheral blood levels of two or three blood cell lines.Treatment options mainly include immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation.The primary advantage of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the availability of a donor for nearly everyone.With ongoing improvements in conditioning regimens, haploidentical hematopoietic stem cell transplantation has made significant progress.This paper aims to review the research progress on haplo-HSCT for treating acquired SAA in children, providing reference for clinical practice.

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

Objective:To summarize and analyze the clinical characteristics of pediatric pulmonary hypertension (PH) and the related factors affecting the prognosis，to provide a basis for the early diagnosis and treatment of the disease.Methods:The clinical data of 80 PH children hospitalized in the intensive care department of Children's Hospital of Capital Pediatric Research Institute from January 1,2019 to December 31,2022 were retrospectively analyzed,and general data,clinical symptoms, echocardiography, laboratory examination and treatment indicators were collected. According to survival death groups, multivariate Logistic regression was applied to analyze independent associated risk factors for PH death.Results:（1）Clinical characteristics of childhood PH: more common in infants, the average age of treatment was 0.9(0.3-5.3)years, the male to female ratio was 1.3∶1, and the average time from first symptoms to first diagnosis was 6.5 (2,14) days. The etiology of PH in children was complex, with arterial PH (PAH) (40%), pulmonary disease and(or) hypoxia (33.8%) being the most common. The main clinical manifestations were dyspnea, decreased activity endurance, poor appetite, and positive heart examination. Severe PH accounted for 53.8%, 30% of pulmonary hypertensive crisis.（2）Factors affecting the prognosis of childhood PH: childhood PH mortality was 20.8%, compared with the survival group, ICU length of stay, loss of appetite, decreased urine volume, cardiac function classification, right heart size, main pulmonary artery diameter/ascending aorta diameter ratio(MPAD/MAD), vasoactive inotropic score(VIS), use of invasive ventilator treatment had statistical significance (all P<0.05). A Logistic regression analysis of death-related factors showed that right heart enlargement ( OR=0.193,95% CI 0.040-0.919, P=0.039), higher MPAD/MAD value ( OR =11.883,95% CI 1.347-104.869, P=0.026), and higher VIS score ( OR= 1.029,95% CI 1.003-1.056, P=0.028) were independent risk factors for poor prognosis. Conclusion:（1）Children PH is mainly infants, the causes of PAH and pulmonary diseases, severe PH accounted for 53.8%, 30% of which have pulmonary hypertensive crisis.（2）An enlarged right heart, higher MPAD/MAD values, and higher VIS score are independent risk factors for death in children with PH.

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

Objective:To summarize and analyze the clinical characteristics of pediatric pulmonary hypertension (PH) and the related factors affecting the prognosis，to provide a basis for the early diagnosis and treatment of the disease.Methods:The clinical data of 80 PH children hospitalized in the intensive care department of Children's Hospital of Capital Pediatric Research Institute from January 1,2019 to December 31,2022 were retrospectively analyzed,and general data,clinical symptoms, echocardiography, laboratory examination and treatment indicators were collected. According to survival death groups, multivariate Logistic regression was applied to analyze independent associated risk factors for PH death.Results:（1）Clinical characteristics of childhood PH: more common in infants, the average age of treatment was 0.9(0.3-5.3)years, the male to female ratio was 1.3∶1, and the average time from first symptoms to first diagnosis was 6.5 (2,14) days. The etiology of PH in children was complex, with arterial PH (PAH) (40%), pulmonary disease and(or) hypoxia (33.8%) being the most common. The main clinical manifestations were dyspnea, decreased activity endurance, poor appetite, and positive heart examination. Severe PH accounted for 53.8%, 30% of pulmonary hypertensive crisis.（2）Factors affecting the prognosis of childhood PH: childhood PH mortality was 20.8%, compared with the survival group, ICU length of stay, loss of appetite, decreased urine volume, cardiac function classification, right heart size, main pulmonary artery diameter/ascending aorta diameter ratio(MPAD/MAD), vasoactive inotropic score(VIS), use of invasive ventilator treatment had statistical significance (all P<0.05). A Logistic regression analysis of death-related factors showed that right heart enlargement ( OR=0.193,95% CI 0.040-0.919, P=0.039), higher MPAD/MAD value ( OR =11.883,95% CI 1.347-104.869, P=0.026), and higher VIS score ( OR= 1.029,95% CI 1.003-1.056, P=0.028) were independent risk factors for poor prognosis. Conclusion:（1）Children PH is mainly infants, the causes of PAH and pulmonary diseases, severe PH accounted for 53.8%, 30% of which have pulmonary hypertensive crisis.（2）An enlarged right heart, higher MPAD/MAD values, and higher VIS score are independent risk factors for death in children with PH.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.