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.

BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.

BACKGROUND:Bone marrow mesenchymal stem cells are one of the sources of adipocytes and express all renin-angiotensin system components,but the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue is not clear.OBJECTIVE:To observe the effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipose tissue and investigate the role of angiotensin 1a receptor knockout in effect of angiotensin Ⅱ on bone marrow mesenchymal stem cell differentiation into brown adipocytes and its potential mechanisms.METHODS:After isolation and culture of bone marrow mesenchymal stem cells in wild-type and angiotensin 1a receptor knockout SD rats,the cells were cultured to the third generation and randomly divided into four groups:wild type group,knockout group,wild type+angiotensin Ⅱ group,and knockout+angiotensin Ⅱ group.The differentiation was induced in the brown fat induced differentiation medium for 14 days.Angiotensin Ⅱ(100 nmol/L)was added for intervention when the differentiation medium was changed each time in the latter two groups.Western blot assay,qRT-PCR,immunofluorescence,and other methods were used to detect the expression of induced differentiation,lipolysis,β oxidation,and mitochondrial biogenesis in brown fat.RESULTS AND CONCLUSION:Angiotensin Ⅱ could inhibit the browning of rat bone marrow mesenchymal stem cells.Knockout of angiotensin 1a receptor could improve the inhibitory effect of angiotensin Ⅱ on brown lipid formation of rat bone marrow mesenchymal stem cells by promoting lipolysis,enhancing fatty acid β oxidation,promoting mitochondrial biogenesis,and enhancing mitochondrial function.These findings provide new research directions and potential therapeutic targets for obesity treatment,revealing the important role of renin angiotensin systems in fat metabolism and its potential as a therapeutic target.

Objective:To summarize the clinical characteristics of newly-developed lesions of early esophageal cancer and precancerous lesions after endoscopic submucosal dissection (ESD) , and to investigate the risk factors associated with metachronous multiple primary early esophageal cancers.Methods:A retrospective analysis was conducted on clinical data and postoperative follow-up results of 311 patients who underwent esophageal ESD at the Department of Gastroenterology, Taizhou People's Hospital, from January 2018 to January 2020. The incidence and interval of newly-developed lesions were documented, and the risk factors for metachronous multiple primary esophageal cancers were identified.Results:Among the 311 patients, 1 case (0.3%) experienced local recurrence, 2 patients (0.6%) had synchronous multiple primary early esophageal cancers, and 27 cases (8.7%) had metachronous multiple primary early esophageal cancers. Multivariate regression analysis showed that lesion length ( OR=5.728, 95% CI: 0.959-34.208, P<0.001), Lugol-voiding lesions (LVLs) with speckled distribution ( OR=6.574, 95% CI: 2.163-19.977, P<0.001), and high neutrophil-to-lymphocyte ratio (NLR) ( OR=3.72, 95% CI: 2.144-6.452, P<0.001) were independent risk factors for metachronous multiple primary early esophageal cancers. Conclusion:Incidence of metachronous multiple primary early esophageal cancers is elevated in patients with long lesions, LVLs exhibiting speckled distribution, and high NLR. Therefore, close follow-up is essential for patients displaying these identified risk factors.

Purpose To explore the application value of combining 18F-FDG PET images with interpretable deep learning radiomics(IDLR)models in the differential diagnosis of primary Parkinson's disease(IPD)and atypical Parkinson's syndrome.Materials and Methods This cross-sectional study was conducted using the Parkinson's Disease PET Imaging Benchmark Database from Huashan Hospital,Fudan University from March 2015 to February 2023.A total of 330 Parkinson's disease patients underwent 18F-FDG PET imaging,both 18F-FDG PET imaging and clinical scale information were collected for all subjects.The study included two cohorts,a training group(n=270)and a testing group(n=60),with a total of 211 cases in the IPD group,59 cases in the progressive supranuclear palsy(PSP)group,and a group of 60 patients with multiple system atrophy(MSA).The clinical information between different groups were compared.An IDLR model was developed to extract feature indicators.Under the supervision of radiomics features,IDLR features were selected from the features collected by neural network extractors,and a binary support vector machine model was constructed for the selected features in images of in testing group.The constructed IDLR model,traditional radiomics model and standard uptake ratio model were separately used to calculate the performance metrics and area under curve values of deep learning models for pairwise classification between IPD/PSP/MSA groups.The study conducted independent classification and testing in two cohorts using 100 10-fold cross-validation tests.Brain-related regions of interest were displayed through feature mapping,using gradient weighted class activation maps to highlight and visualize the most relevant information in the brain.The output heatmaps of different disease groups were examined and compared with clinical diagnostic locations.Results The IDLR model showed promising results for differentiating between Parkinson's syndrome patients.It achieved the best classification performance and had the highest area under the curve values compared to other comparative models such as the standard uptake ratio model(Z=1.22-3.23,all P<0.05),and radiomics model(Z=1.31-2.96,all P<0.05).The area under the curve values for the IDLR model in differentiating MSA and IPD were 0.935 7,for MSA and PSP were 0.975 4,for IPD and PSP were 0.982 5 in the test set.The IDLR model also showed consistency between its filtered feature maps and the visualization of gradient-weighted class activation mapping slice thermal maps in the radiomics regions of interest.Conclusion The IDLR model has the potential for differential diagnosis between IPD and atypical Parkinson's syndrome in 18F-FDG PET images.

Background:With the advancement of endoscopic techniques,the detection rate of duodenal lesions has increased,and the selection and curative effect of endoscopic resection of duodenal lesions need to be further explored.Aims:To evaluate the safety and efficacy of endoscopic treatment of duodenal tumors.Methods:A retrospective analysis was conducted on 32 patients with duodenal tumors treated with endoscopic resection from January 2017 to January 2022 at Taizhou People's Hospital Affiliated to Nanjing Medical University.The location,depth,treatment method,postoperative pathology,and complications of duodenal tumors were summarized.Results:Among the 32 patients,there were 21 males and 11 females.Two patients presented with melena,10 patients had abdominal pain,and 20 patients were asymptomatic.Twenty-eight tumors were located in descending part of duodenum,and 4 were located in duodenal bulb.One patient underwent endoscopic submucosal excavation,2 underwent cold snare polypectomy,12 underwent endoscopic submucosal dissection,and 17 underwent endoscopic mucosal resection.All lesions were completely resected.Among the 32 lesions,there were 21 tubular adenoma or tubulovillous adenoma,7 Brunner's gland adenoma,2 lipoma,1 neuroendocrine tumor,and 1 stromal tumor.One patient with duodenal tubulovillous adenoma had perforation during operation and was transferred to surgery for repair.The other patients did not have complications such as perforation and bleeding during operation.All patients had no recurrence after postoperative endoscopy.Conclusions:Endoscopic treatment for duodenal tumors is safe and effective,and has good clinical value.

Background: The revised Atlanta classification (RAC) and determinant-based classification (DBC) are widely used in assessing the severity of acute pancreatitis (AP). However, studies on comparison between RAC and DBC are scarce. Aims: To explore the accuracy of RAC and DBC in the assessment of AP severity. Methods: The clinical data of 481 AP patients from September 2015 to September 2019 at Taizhou People's Hospital were collected and severity were stratified according to RAC and DBC. The treatment and prognosis of each subgroup were compared. Results: On the basis of RAC, 269 (55.9%), 174 (36.2%) and 38 (7.9%) patients were classified as mild AP (MAP), moderate severe AP (MSAP) and severe AP (SAP), respectively. There were significant differences in mortality, ICU monitoring rate, ICU stay, operation rate and hospital stay among the above groups (P<0.05). On the basis of DBC, 319 (66.3%), 117 (24.3%), 34 (7.1%) and 11 (2.3%) patients were classified as MAP, MSAP, SAP and critical AP (CAP), respectively. There were significant differences in mortality, ICU monitoring rate, ICU stay, operation rate and hospital stay among the above groups (P<0.05). The ICU monitoring rate (100% vs. 63.2%, P=0.014), median ICU stay (35 days vs. 15 days, P=0.001), hospital stay [(50.36±21.54) days vs. (22.78±14.56) days, P=0.038] were significantly increased in CAP patients (classified by DBC) than those in SAP patients (classified by RAC), however, no significant differences in mortality and operation rate were found between the two groups (P=0.136; P=0.202). Conclusions: Both RAC and DBC can accurately stratify the severity of AP. SAP patients (classified by RAC) complicated with infected necrosis should be further classified into CAP.

Objective:To study the distribution and related factors of aggressive behavior among school aged children in Nanjing.Methods:Totally 4678 primary school students in Nanjing were sampled by cluster random sampling in this study.The General questionnaire and Achenbach's child Behavior Checklist were used to investi gate the general situation and aggressive behavior.Results:The rate of aggressive behavior of school-age children in Nanjing was 3.6 ％ (167/4678).Multivariate logistic regression analysis indicated that democratic parenting style [other parenting styles (OR =1.94,95％ CI =1.10-3.42),mixed parenting style(OR =1.96,95％ CI =1.35-2.85)],and genetic screening before birth (OR =0.71,95％ CI =0.52-0.99) were protective factors for children's aggressive behavior.The factor figures of aggressive behavior were positively correlated with that of oth er behavior problems in Pearson correlation analysis (r =0.52-0.80,Ps ＜0.01).Conclusion:About 3.6％ of the school aged children in Nanjing have aggressive behavior.It is more likely to have aggressive behaviors for children who is in other parenting styles except the democratic style and never have the genetic screening before birth.And children who with aggressive behavior may co-occur with other behavior problems.

Objective:To analyze the curative effect and prognostic factors for comprehensive therapy in patients with high-grade glioma.Methods:Patients with high-grade glioma (WHO grade Ⅲ,grade Ⅳ) were chosen from July 2008 to May 2016 in the Hunan Cancer Hospital,and a retrospective analysis was performed in 64 patients with complete follow-up data.Results:The follow-up time was 3-111 (median 29.5) months,the median overall survival time was 36.00 (95％ CI 22.85 to 49.16) months,the median progression-free survival time (PFS) was 21.00 (95％ CI 9.72 to 32.28) months,The 1-year,2-year,3-year and 5-year survival rates of high-grade glioma patients were 87.50％,56.25％,40.63％ and 17.19％,respectively.The univariate analysis of Log-Rank test and the Cox regression model analysis showed that the prognostic factors related to the prognosis of high-grade glioma patients were pathological grade,resection degree,and concurrent chemo-radiotherapy (P＜0.05).Conclusion:The overall survival time,progression-free survival time and the 5-year survival rate of patients with high-grade glioma after comprehensive treatment is partially improved.The factors relevant to the prognosis of patients with high-grade glioma are pathological grade,resection degree,and concurrent chemo-radiotherapy,indicating that the glioma patients (WHO grade Ⅲ) received total resection of the tumor and concurrent chemo-radiotherapy have better clinical effect.

After the initial episode of acute pancreatitis (AP), some patients have a tendency to relapse.With the development of imaging technologies and genetic tests, the diagnostic accuracy of the etiological factors of recurrent acute pancreatitis (RAP) such as dysfunction of sphincter of Oddi, pancreas divisum, and genetic mutations are improved.Clinical studies indicate that etiological treatment by endoscopic approaches may reduce recurrence in some RAP patients.In this article, the progress in etiology, diagnosis and treatment of RAP was reviewed.