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.

ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange （LPE） in patients with acute-on-chronic liver failure （ACLF）. MethodsA prospective cohort study was designed， and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment， the patients in the DPMAS+LPE group received DPMAS and LPE treatment， and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results， liver function parameters， renal function markers， electrolytes， coagulation function parameters， cytokines， adverse events， and 28-day prognosis before surgery （baseline）， during surgery （DPMAS or CA280）， and after surgery （after sequential LPE treatment）. The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group， and the independent-samples t test was used for comparison between groups； the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group， and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups， and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment， the ACLF patients had significant reductions in the levels of cytokines （IL-6， IL-8， IL-10， TNF-α， and IFN-γ）， liver function parameters （ALT， AST， ALP， TBil， DBil， Alb， and glutathione reductase）， and the renal function marker urea nitrogen （all P<0.05）， and in terms of coagulation function parameters， there were significant increases in prothrombin time， activated partial thromboplastin time （APTT）， thrombin time， and international normalized ratio （INR） and significant reductions in prothrombin activity （PTA） and fibrinogen （FIB） （all P<0.05）. Compared with the DPMAS+LPE group， the CA280+LPE group showed better improvements in the serum cytokines IL-8 （Z=-2.63， P=0.009）， IL-10 （Z=-3.94， P<0.001）， and TNF-α （Z=-1.53， P=0.023）， and the two artificial liver support systems had a similar effect in improving liver function （ALT， AST， GGT， GR， TBil， and DBil） （all P >0.05）， but the CA280+LPE group showed a significantly greater reduction in Alb （Z=-2.08， P=0.037）. CA280+LPE was more effective in reducing uric acid （Z=-2.97， P=0.003）. Compared with DPMAS+LPE， CA280+LPE treatment resulted in a significant reduction in INR （Z=-4.01， P<0.001）， a significant increase in APTT （Z=-2.53， P=0.011）， and significant greater increases in PTA （Z=-6.28， P<0.001） and FIB （Z=-3.93， P<0.001）. There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups （all P>0.05）. The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC （r=0.22， P=0.042）， TBil （r=0.29， P=0.005）， and FIB （r=-0.33， P=0.003）； IL-8 was positively correlated with APTT （r=0.37， P<0.001） and INR （r=0.25， P=0.013）； TNF-α was significantly correlated with WBC （r=0.40， P<0.001） and TBil （r=0.34， P<0.001）. ConclusionCompared with DPMAS， CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients， but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients， but further studies are needed to verify its long-term efficacy.

Objective:To compare the chemical composition of decoction and granules of Sangju Decoction; To provide a method for quality evaluation of Sangju Decoction.Methods:HPLC was used to establish fingerprints, and a comprehensive comparative study was conducted on the traditional decoction and formula granules of Sangju Decoction from four aspects: chemical composition type, fingerprint similarity, chemical pattern recognition analysis, and representative index component content.Results:The fingerprint similarity of the 10 batches of traditional decoction was >0.988. 35 peaks were identified and 12 peaks were identified as common peaks (neochlorogenic acid for peak 7, chlorogenic acid for peak 10, cryptochlorogenic acid for peak 11, 1,3-dicaffeoylquinic acid for peak 13, rutin for peak 17, lenoside A for peak 19, lignan for peak 20, isochlorogenic acid B for peak 24, ammonium glycyrrhizate for peak 25). The fingerprint similarity of the formulation pellets was >0.983, and 29 characteristic peaks were identified. Compared with the traditional decoction, some batches of the granules lacked peaks 14, 26, 27, 30, 32 and 34, and clustering analysis (CA), principal component analysis (PCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) could distinguish between the two. The contents of the 10 index components neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 1,3-dicaffeoylquinic acid, forsythia ester glycoside A, grass glycosides, isochlorogenic acid B, 3,5-O-dicaffeoylquinic acid, forsythia glycosides, monkshood glycosides in the traditional soup were higher than that in the granules, and the contents of rutin and ammonium glycyrrhizate in the granules were higher than that in traditional decoction.Conclusions:The content and composition of traditional decoction and formula granules of Sangju Decoction are significantly different. The combination of fingerprinting and chemical pattern identification effectively can effectively evaluate the difference between traditional decoction and formula granules of Sangju Decoction, which can lay a foundation for the quality control and rational clinical application of formula granules of Sangju Decoction.

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.
Humans ; Signal Transduction ; Interferon Type I/metabolism* ; Ossification of Posterior Longitudinal Ligament/genetics* ; Gene Expression Profiling ; Single-Cell Analysis ; Osteogenesis/genetics* ; Receptor, Interferon alpha-beta/metabolism* ; Male ; Female ; Cell Differentiation ; Middle Aged

Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (eculizumab, inebilizumab, and satralizumab). Neurol Neuroimmunol Neuroinflamm published international Delphi consensus on the management of AQP4-IgG+ NMOSD in May 31, 2023. Twenty-five statements reached consensus after two voting rounds by 24 Delphi panel experts. Inebilizumab and satralizumab have been listed in China, and off-label immunosuppressants and biologics are also used in clinical practice. However, there are no standard treatment recommendations in use of these biologics and maintenance therapy of NMOSD. Therefore, the interpretation of this consensus, focusing on the initial use of monoclonal drugs, the conversion between monoclonal drugs and immunosuppressants, as well as the application and safety of special populations, is conducive to improving the normative and effective use of of monoclonal drugs in NMOSD y ophthalmologists and neurologists

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a chronic functional bowel disorder characterized by abdominal pain and diarrhea， with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders， especially IBS-D. 5-Hydroxytryptamine （5-HT）， as an important brain-gut peptide regulating gastrointestinal function， affects brain activity， gastrointestinal motility， pain perception， mucosal inflammation， and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years， traditional Chinese medicine （TCM） has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM， this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway， aiming to provide a scientific basis for TCM treatment of this disease.

Objective:To summarize and analyze the efficacy, experience and follow-up results of 300 cases of transposition of the great arteries (TGA) intervened by arterial switch operation.Methods:It was a retrospective, single-center study involving 300 TGA patients intervened by arterial switch operation between January 2010 and December 2017 in Guangdong Provincial People′s Hospital.Their clinical data were retrospectively analyzed.There were 236 male patients and 64 females.Among them, 128 cases (42.7%) were TGA with ventricular septal defect (TGA/VSD), and 172 cases (57.3%) were TGA with intact ventricular septal defect (TGA/IVS). The mean age and weight at operation were (23.8±39.2) cases days, and (3.5±0.8) kg, respectively.There were 193 cases (64.3%) with usual coronary artery patterns, and 107 cases (35.7%) with unusual coronary artery patterns.Among the 107 cases with unusual coronary artery patterns, 21 cases (7.0%) were involved with the intramural coronary artery, and 17 (5.7%) presented the single-ostium coronary pattern.Non normal distribution data were used the Mann- Whitney U test.Categorical measures were compared by Chi- square test or Fisher′ s exact test.Survival probability and freedom from events were calculated by the Kaplan-Meier method, and difference in survival probability by the Log Rank test. Results:All patients were successfully intervened by arterial switch operation, 73.3% of patients with TGA/IVS underwent the surgery within 3 weeks after birth, and 85.9% of patients with TGA/VSD underwent surgery within 3 months.The mean cardiopulmonary bypass time and aortic occlusion time were (193±68) min, and (122±39) min, respectively.Twenty-five patients (8.3%) died in hospital.Thirty cases had low cardiac output syndrome, 1 implanted with a permanent pacemaker due to complete atrioventricular block.A total of 254 patients were followed up for 1 month to 10 years.Three patients with single-ostium coronary pattern died at the follow-up period.The 5-year and 10-year survival rates were both 90.7%.During the follow-up, 49 cases (49/254 cases, 19.3%) had pulmonary artery stenosis, 66 cases (66/254 cases, 26.0%) had aortic valve regurgitation, 47 cases (47/254 cases, 18.5%) had pulmonary valve regurgitation, and 4 (4/254 cases, 1.6%) had aortic anastomotic stenosis.Among the 21 patients (21/254 cases, 8.3%) requiring reintervention, 17 patients (17/254 cases, 6.7%) underwent a total of 18 reinterventions, including 12 interventions of pulmonary artery plasty, 4 of percutaneous balloon pulmonary valvuloplasty, 1 of aortic reconstruction at anastomosis and 1 of pacemaker exchange due to battery exhaustion.Conclusions:Arterial switch operation is the optimal treatment for TGA.The long-term follow-up results of arterial switch operation are satisfactory in TGA children, with a low risk of long-term reoperation.

【Objective】 To construct an in-vitro model of erythrocyte antibody-mediated complement activation, and establish quantitative detection methods based on flow cytometry and spectrophotometry, so as to explore the correlation of anti-body titers and complement activation speed, and provide a methodological basis for studying the adverse transfusion reactions of anti-body mediated complement hemolysis. 【Methods】 Mouse monoclonal antibody that recognized human C3b and fluorescent secondary antibody were used to label C3b fragments on erythrocytes, and the deposition of C3b fragments after complement activation was detected by flow cytometry. The absorbance at 540 nm of the supernatant in the complement activation reaction system was measured by spectrophotometry as the amount of hemoglobin released was related to the absorbance. 【Results】 The complement activation system was constructed according to the ratio of 3% red blood cell suspension (mixed for 6 people) 1∶anti-Tj^a 1∶complement 2. The repeatability was good (P value>0.05) as different red blood cell mixtures had been used to repeat the detection reaction system. When using 32×, 64× and 128× dilutions of anti-Tj^a mediated complement activation, the deposition of C3b fragments has been detected by flow cytometry at 30 s, 1 min and 2 min, respectively, and MFI peaked at 5 min, 10 min and 30 min, respectively. No obvious hemolysis has been observed within 1.5 h. 【Conclusion】 In vitro model of anti-Tj^a-mediated complement activation demonstrates the speed of complement activation is related to the concentration of antibody. At a certain antibody concentration, the speed of complement activation has been slowed down, and no obvious hemolysis observed.

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of Scimitar syndrome.Methods:A retrospective analysis of clinical data of 13 children with scimitar syndrome from January 2013 to November 2020, including clinical symptoms, chest X-ray, echocardiography, cardiac CT and cardiac catheterization prognosis and follow-up.Results:13 children with scimitar syndrome were diagnosed, including 7 girls and 6 boys with a average age of 17 months(21 days to 10 years).3 cases <5 kg in weight. Ten patients presented with the infantile form and 3 with the adult form of scimitar syndrome. 13 infantile form had lower respiratory tract infections, heart failure, and growth retardation, of which 8 cases were with severe pulmonary arterial hypertension. 3 adult form were diagnosed because of heart murmur. 12 cases had coexisting cardiac lesions, including 12 atrial septal defect, 2 patent ductus arteriosus, 1 right ventricular double outlet/ventricular septal defect, 4 right lung and right pulmonary artery dysplasia, 2 right lung dysplasia, 6 additional systemic arterial supply to the right lung. Ten patients had pulmonary venous drainage correction surgery, one patient only underwent right ventricular double-outlet correction, three patients died of severe pulmonary hypertension; one patient lost the opportunity of surgery due to obstructive pulmonary hypertension, and one patient was complicated by nervous system The disease gave up treatment. One corrected case was stenosed during discharge and 2 corrected children became stenotic during follow-ups.Conclusion:Found with the median or dextrocardial heart, recurrent respiratory infections, or unexplained pulmonary hypertension, the possibility of scimitar syndrome should be considered. The combination of echocardiography and cardiac CTA can confirm the diagnosis as soon as possible. The risk factors for mortality included infantile form and severe preoperative pulmonary hypertension. Long-term follow-up is still required after operation, and surgical intervention is required again if necessary.

Animals ; CRISPR-Cas Systems ; Gene Editing ; Humans