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 investigate the effects of Jiawei Ditan Decoction on neurological function,pentraxin-3(PTX-3),and vascular endothelial growth factor(VEGF)in patients with post-ischemic stroke cognitive impairment(PSCI).Methods A total of 97 patients with PSCI who were admitted to Xuzhou Central Hospital from March 2022 to March 2024 were enrolled and randomly assigned to control group(n=48)or decoction group(n=49)using the envelope drawing method.The control group received conventional treatment,while the decoction group was additionally treated with Jiawei Ditan Decoction.Clinical efficacy,Traditional Chinese Medicine(TCM)syndrome scores,cognitive and functional assessments,laboratory markers,and oxidative stress levels were compared between the two groups.Results The total effective rate in the decoction group was significantly higher than that in the control group(P<0.05).At 3 and 6 months after treatment,TCM syndrome scores in the decoction group were lower than those in the control group(P<0.05).The scores of the Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE),and Barthel index(BI)in the decoction group were higher than those in the control group at 3 months after treatment,while the National Institutes of Health stroke scale(NIHSS)score in the decoction group was lower than that in the control group(P<0.05).At 1 month after treatment,PTX-3 and hypersensitive C-reactive protein(hs-CRP)levels in the decoction group were lower than those in the control group,while VEGF,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and nitric oxide(NO)levels in the decoction group were higher than those in the control group(P<0.05).Conclusion Jiawei Ditan Decoction exhibits significant effects on improving neurological function and modulating PTX-3 and VEGF levels in patients with PSCI.

Objective To establish a rapid and accurate droplet digital PCR(ddPCR)detection method for detecting Staphylococcus aureus(SA)in laboratory animals and the environment.Methods Using the heat-stable nuclease gene(nuc)of SA as the target gene,a pair of specific primers and probes are designed within its conserved region.Optimize the reaction conditions,test the dynamic range,and evaluate the specificity and stability of the method.Using the same template,test reactions were performed with both ddPCR and real-time quantitative PCR(qPCR)method to assess the interchangeability between the two approaches.Finally,the method is applied to the detection of various clinical samples.Results The kinetic range of the established SA ddPCR method is 100～15 000 copies/μL,with a detection limit of 2.5 copies and a quantification limit of 10 copies;The specificity of this method was tested,and only SA showed positive droplets,while no positive droplets were found for other pathogens;After measuring three parallel samples,the standard deviation and relative standard deviation were calculated.It was found that within the dynamic detection interval of ddPCR,as the target copy number gradually decreased,the relative standard deviation showed an upward trend,but remained below 25％.This result indicates that the detection method has good stability.Conclusions The established ddPCR method for detecting SA has the advantages of high sensitivity,strong specificity,good stability,and good reproducibility.This method can be applied for the detection of SA in laboratory animals.

Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

Liu Baoyi was a famous febrile disease expert in the late Qing Dynasty,who innovated the theory of latent febrile disease.Liu proposed that the deficiency of kidney essence and the deficiency of healthy qi were the prerequisites for the latent cold e-vil,and the exogenous cold evil was the inducement of the disease.He advocated the treatment of latent febrile disease based on the six meridians,with the two ideas of eliminating evil qi and strengthening healthy qi as the outline,and the general principle of treatment was to relieve heat,nourish yin and expel evil qi.He attached importance to the coordination of medicine and food,made good use of fresh medicine,attached importance to drug processing,emphasized the use of herb processed by herb,and adapted the medicine ac-cording to the syndromes.He preferred to use co-processed products for clinical use.The study of Liu's academic thoughts and medi-cation characteristics in treating latent febrile diseases is of great value in guiding the treatment and medication of various infectious and epidemic diseases with fever characteristics nowadays.

Liu Baoyi was a famous febrile disease expert in the late Qing Dynasty,who innovated the theory of latent febrile disease.Liu proposed that the deficiency of kidney essence and the deficiency of healthy qi were the prerequisites for the latent cold e-vil,and the exogenous cold evil was the inducement of the disease.He advocated the treatment of latent febrile disease based on the six meridians,with the two ideas of eliminating evil qi and strengthening healthy qi as the outline,and the general principle of treatment was to relieve heat,nourish yin and expel evil qi.He attached importance to the coordination of medicine and food,made good use of fresh medicine,attached importance to drug processing,emphasized the use of herb processed by herb,and adapted the medicine ac-cording to the syndromes.He preferred to use co-processed products for clinical use.The study of Liu's academic thoughts and medi-cation characteristics in treating latent febrile diseases is of great value in guiding the treatment and medication of various infectious and epidemic diseases with fever characteristics nowadays.

Objective To establish a rapid and accurate droplet digital PCR(ddPCR)detection method for detecting Staphylococcus aureus(SA)in laboratory animals and the environment.Methods Using the heat-stable nuclease gene(nuc)of SA as the target gene,a pair of specific primers and probes are designed within its conserved region.Optimize the reaction conditions,test the dynamic range,and evaluate the specificity and stability of the method.Using the same template,test reactions were performed with both ddPCR and real-time quantitative PCR(qPCR)method to assess the interchangeability between the two approaches.Finally,the method is applied to the detection of various clinical samples.Results The kinetic range of the established SA ddPCR method is 100～15 000 copies/μL,with a detection limit of 2.5 copies and a quantification limit of 10 copies;The specificity of this method was tested,and only SA showed positive droplets,while no positive droplets were found for other pathogens;After measuring three parallel samples,the standard deviation and relative standard deviation were calculated.It was found that within the dynamic detection interval of ddPCR,as the target copy number gradually decreased,the relative standard deviation showed an upward trend,but remained below 25％.This result indicates that the detection method has good stability.Conclusions The established ddPCR method for detecting SA has the advantages of high sensitivity,strong specificity,good stability,and good reproducibility.This method can be applied for the detection of SA in laboratory animals.

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