Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective To investigate the correlation of sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2a(SERCA2a)and blood urea nitrogen(BUN)to albumin(ALB)ratio(BAR)with cardiac function and prognosis in patients with chronic heart failure(CHF).Methods A total of 200 CHF patients admitted to this hospital from January 2021 to January 2023 were selected as the CHF group and 100 healthy people un-dergoing physical examination as the control group.CHF patients were divided into class Ⅰ group(38 cases),class Ⅱ group(40 cases),class Ⅲ group(54 cases)and class Ⅳ group(68 cases)according to the New York Heart Association(NYHA)cardiac function classification after admission.According to the prognosis,they were divided into poor prognosis group(60 cases)and good prognosis group(140 cases).Serum SERCA2a BUN,ALB levels were measured and BAR was calculated.Spearman rank correlation coefficient was used to analyze the correlation between serum SERCA2a,BAR and NYHA cardiac function classification in CHF pa-tients.Taking the prognosis of CHF patients as the dependent variable,a multivariate unconditional Logistic regression model was established to determine its influencing factors.Receiver operating characteristic curve was drawn to evaluate the predictive value of serum SERCA2a and BAR for poor prognosis of CHF patients.Results Compared with the control group,the serum SERCA2a level was decreased and BAR was increased in the CHF group(P＜0.05).The level of SERCA2a in class Ⅰ group,class Ⅱ group,class Ⅲ group and classⅣ group decreased and BAR increased successively(P＜0.05).The NYHA classification was negatively cor-related with serum SERCA2a level(rs=-0.756,P＜0.05),and positively correlated with BAR(rs=0.722,P＜0.05).After 1-year follow-up,the incidence of poor prognosis in 200 CHF patients was 30.00％(60/200).Increased NYHA class(OR=1.936,95％CI:1.115-3.364),atrial fibrillation(OR=3.269,95％CI:1.078-9.913),N-terminal pro-B-type natriuretic peptide(OR=1.002,95％CI:1.001-1.009)and BAR(OR=1.169,95％CI:1.082-1.263)were independent risk factors for poor prognosis in patients with CHF(P＜0.05),increased left ventricular ejection fraction(OR=0.810,95％CI:0.716-0.916)and SERCA2a(OR=0.964,95％CI:0.947-0.981)were independent protective factors(P＜0.05).The area under the curve of serum SERCA2a combined with BAR to predict the poor prognosis of CHF patients was 0.865(95％CI:0.810-0.910),which was larger than 0.784(95％CI:0.720-0.839)and 0.777(95％CI:0.713-0.833)predicted by serum SERCA2a and BAR levels alone,and the difference was statistically significant(Z=2.944,3.250,P＜0.05).Conclusion The decrease of SERCA2a and the increase of BAR are closely re-lated to cardiac function and prognosis in patients with CHF.Serum SERCA2a combined with BAR has a higher value in predicting poor prognosis in patients with CHF.

Objective To study the chemical composition of and identify its active components.Methods The chemical constituents of Dendrobium Primulinum were extracted using solvents,followed by separation through silica gel and gel column chromatography,with structural identification performed via spectral analysis.The in vitro activity screening of some compounds was conducted using the MTT assay.Results Seven compounds were isolated and identified from Dendrobium primulinum,namely 7-dihydroxy-2,4-methoxyphenanthrene(1),densiflorol B(2),3,4,7-trihydroxy-2-methoxy-9,10-dihydrophenanthrene(3),thunalbene(4),phillygenin(5),3 β-hydroxy-5 α,8 α-epidioxyergosta-6,22-diene(6)、4-hydroxy-3,5-dimethoxy--cinnamaldehyde(7).Antitumor activity tests were performed on compounds 1 to 5,revealing that compound 1 exhibited strong inhibitory activity against the MCF-7/S cell line,with an IC50 of 5.13 μM.Conclusion Compounds 1 to 6 are reported for the first time from Dendrobium primulinum,while compound 7 is reported for the first time from this genus.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Objective To discuss the potential mechanisms by which programmed cell death(PCD)might contribute to the pathogenesis of diabetic kidney disease(DKD).Methods Retrieve the datasets GSE30529 and GSE30122 from the Gene Expression Omnibus database and analyze them to obtain differentially expressed genes(DEGs)associated with DKD.Utilize the Gene Set Enrichment Analysis website,the ferroptosis database,and the autophagy database,along with relevant literature,to identify genes associated with apoptosis,necroptosis,pyroptosis,autophagy,and ferroptosis.Cross-reference these genes with the DKD DEGs to identify PCD-related genes that are differentially expressed in DKD.Perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to explore the biological functions and potential pathways of the core genes.Conduct a protein-protein interaction network analysis to examine the interaction relationships of the target genes,and use the CytoHubba plugin in Cytoscape to screen for Hub genes.Results In the GSE30529 dataset,a total of 460 DEGs were identified,while the GSE30122 dataset yielded 992 DEGs.After merging and removing duplicates,932 DEGs were obtained.By intersecting these DEGs with PCD-related genes,61 apoptosis-related genes,7 necroptosis-related genes,39 pyroptosis-related genes,18 autophagy-related genes,and 16 ferroptosis-related genes associated with DKD were identified.The KEGG analysis results indicated that the DEGs related to apoptosis,necroptosis,pyroptosis,and autophagy in PCD were primarily enriched in pathways associated with diabetic complications,including the AGE-RAGE,IL-17,NF-κB,and TNF signaling pathways.In contrast,DEGs related to ferroptosis were mainly enriched in the fatty acid degradation pathway.GO enrichment analysis revealed that the biological processes of the differentially expressed PCD related genes in DKD were primarily involved in the regulation of signals such as NF-κB-inducing kinase/NF-κB,IL-1,and IL-17.Conclusions Differentially expressed PCD-related genes in DKD are mainly enriched in related signal pathways such as AGE-RAGE,IL-17,NF-κB and TNF,suggesting a critical role of PCD in the pathogenesis of DKD.

Objective:To analyze the risk factors for prolonged hospital stay in inpatients based on data from nutritionDay worldwide survey 2020 to 2022 conducted in China and to construct and validate a prediction model for clinical decision-making.Methods:This study was a retrospective study, the data source was the China's multi-centered nutritionalDay worldwide database for nutrition status in inpatients. A total of 2 335 cases registered in the database from 2020 to 2022 were selected for the study, comprising individuals aged 18 and above, with valid response for the 30-day prognosis questionnaires, and with complete clinical data. The demographic characteristics, nutrition-related indicators, disease information, and outcome indicators of the participants were collected. Based on the 75th percentile of hospitalization duration, the participants were divided into the prolonged length of stay group (570 cases) and the normal length of stay group (1 765 cases). A nomogram prediction model was constructed using the least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Logistic regression analysis. Area under the curve ( AUC), calibration curve, Hosmer-Lemeshow test, and clinical decision curve were used to verify discriminative ability, goodness-of-fit, and clinical effectiveness of the model. Results:Seven independent risk factors for prolonged length of stay were identified, namely body mass index (BMI), whether surgery occurred during hospitalization, intensive care unit admission during hospitalization, Nutrition Risk Screening 2002 score, ambulatory independence, previous hospitalization frequency, and weight loss in the past 3 months. A nomogram prediction model was established accordingly. The AUC of training set was 0.783 (95% CI: 0.759 - 0.807), and the AUC of validation set was 0.797 (95% CI: 0.746 - 0.849). Calibration curves and Hosmer-Lemeshow tests ( P=0.735 for training set, P=0.431 for validation set) indicated good model fitting. The clinical decision curve demonstrated the favorable clinical utility of the nomogram. Conclusions:BMI, whether they had surgery during hospitalization, whether they were admitted to the ICU during hospitalization, NRS 2002 score, whether they were able to walk independently, number of previous hospitalizations, and weight loss in the past 3 months were risk factors for longer stay in Chinese hospitalized patients. The nomogram prediction model developed in this study can forecast the risk of prolonged length of stay among Chinese inpatients, providing a basis for early identification and intervenion in high-risk patients.

Objective:To analyze the risk factors for prolonged hospital stay in inpatients based on data from nutritionDay worldwide survey 2020 to 2022 conducted in China and to construct and validate a prediction model for clinical decision-making.Methods:This study was a retrospective study, the data source was the China's multi-centered nutritionalDay worldwide database for nutrition status in inpatients. A total of 2 335 cases registered in the database from 2020 to 2022 were selected for the study, comprising individuals aged 18 and above, with valid response for the 30-day prognosis questionnaires, and with complete clinical data. The demographic characteristics, nutrition-related indicators, disease information, and outcome indicators of the participants were collected. Based on the 75th percentile of hospitalization duration, the participants were divided into the prolonged length of stay group (570 cases) and the normal length of stay group (1 765 cases). A nomogram prediction model was constructed using the least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate Logistic regression analysis. Area under the curve ( AUC), calibration curve, Hosmer-Lemeshow test, and clinical decision curve were used to verify discriminative ability, goodness-of-fit, and clinical effectiveness of the model. Results:Seven independent risk factors for prolonged length of stay were identified, namely body mass index (BMI), whether surgery occurred during hospitalization, intensive care unit admission during hospitalization, Nutrition Risk Screening 2002 score, ambulatory independence, previous hospitalization frequency, and weight loss in the past 3 months. A nomogram prediction model was established accordingly. The AUC of training set was 0.783 (95% CI: 0.759 - 0.807), and the AUC of validation set was 0.797 (95% CI: 0.746 - 0.849). Calibration curves and Hosmer-Lemeshow tests ( P=0.735 for training set, P=0.431 for validation set) indicated good model fitting. The clinical decision curve demonstrated the favorable clinical utility of the nomogram. Conclusions:BMI, whether they had surgery during hospitalization, whether they were admitted to the ICU during hospitalization, NRS 2002 score, whether they were able to walk independently, number of previous hospitalizations, and weight loss in the past 3 months were risk factors for longer stay in Chinese hospitalized patients. The nomogram prediction model developed in this study can forecast the risk of prolonged length of stay among Chinese inpatients, providing a basis for early identification and intervenion in high-risk patients.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective To discuss the potential mechanisms by which programmed cell death(PCD)might contribute to the pathogenesis of diabetic kidney disease(DKD).Methods Retrieve the datasets GSE30529 and GSE30122 from the Gene Expression Omnibus database and analyze them to obtain differentially expressed genes(DEGs)associated with DKD.Utilize the Gene Set Enrichment Analysis website,the ferroptosis database,and the autophagy database,along with relevant literature,to identify genes associated with apoptosis,necroptosis,pyroptosis,autophagy,and ferroptosis.Cross-reference these genes with the DKD DEGs to identify PCD-related genes that are differentially expressed in DKD.Perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses to explore the biological functions and potential pathways of the core genes.Conduct a protein-protein interaction network analysis to examine the interaction relationships of the target genes,and use the CytoHubba plugin in Cytoscape to screen for Hub genes.Results In the GSE30529 dataset,a total of 460 DEGs were identified,while the GSE30122 dataset yielded 992 DEGs.After merging and removing duplicates,932 DEGs were obtained.By intersecting these DEGs with PCD-related genes,61 apoptosis-related genes,7 necroptosis-related genes,39 pyroptosis-related genes,18 autophagy-related genes,and 16 ferroptosis-related genes associated with DKD were identified.The KEGG analysis results indicated that the DEGs related to apoptosis,necroptosis,pyroptosis,and autophagy in PCD were primarily enriched in pathways associated with diabetic complications,including the AGE-RAGE,IL-17,NF-κB,and TNF signaling pathways.In contrast,DEGs related to ferroptosis were mainly enriched in the fatty acid degradation pathway.GO enrichment analysis revealed that the biological processes of the differentially expressed PCD related genes in DKD were primarily involved in the regulation of signals such as NF-κB-inducing kinase/NF-κB,IL-1,and IL-17.Conclusions Differentially expressed PCD-related genes in DKD are mainly enriched in related signal pathways such as AGE-RAGE,IL-17,NF-κB and TNF,suggesting a critical role of PCD in the pathogenesis of DKD.