Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal tumor that clinically presents as nodular-type or diffuse-type (D-TGCT). D-TGCT is more aggressive, has a higher surgical recurrence rate, and can potentially lead to severe joint destruction. The traditional treatment is primarily through surgical intervention. Recent advancements in understanding the molecular mechanisms of the disease and the development of new drugs have significantly changed TGCT treatment strategies. Drug therapy and active surveillance have become important treatment options for unresectable or high-recurrence-risk TGCT. Imaging examinations and patient-reported outcome tools play a crucial role in evaluating efficacy and guiding treatment decisions. Comprehensive management by a multidisciplinary team and utilizing individualized treatment plans can significantly improve the quality of life and treatment outcomes of patients. Future research should explore the molecular mechanisms of TGCT, enhance multidisciplinary collaboration, and emphasize long-term management to improve treatment efficacy and patient prognosis.

BACKGROUND:Preliminary research by our group suggests that targeting fibroblast growth factor receptor 1(FGFR1)may be an effective strategy for treating RA. OBJECTIVE:To investigate the effects of an FGFR1 inhibitor(PD173074)on bone destruction in rats with collagen-induced arthritis. METHODS:Twenty-five female Sprague-Dawley rats were randomly divided into five groups:normal control group,model group,methotrexate group,low-dose PD173074 group,and high-dose PD173074 group.Except for the normal control group,rat models of type Ⅱ collagen-induced arthritis were made in each group.After successful modeling,rats were injected intraperitoneally with sterile PBS in the normal and model groups,1.04 mg/kg methotrexate in the methotrexate group,and 5 and 20 mg/kg in the low-dose group and high-dose PD173074 groups,once a week.After 4 weeks of drug administration,clinical symptoms and joint swelling in rats were observed.Micro-CT was used for three-dimensional reconstruction and analysis of the ankle joints.Pathological changes in the ankle joints were observed.Periarticular angiogenesis and the expression of receptor activator of nuclear factor-Κb ligand were detected.The expression levels of p-FGFR1,vascular endothelial growth factor A,and tartrate-resistant acid phosphatase in the synovial membrane were measured.Pathological changes in the liver,spleen,and kidney were observed and liver,spleen,and kidney indices were calculated. RESULTS AND CONCLUSION:PD173074 could alleviate clinical symptoms and joint swelling,delay bone loss,improve bone structure,reduce synovial invasion and cartilage bone erosion,reduce the number of periarticular osteoclasts,inhibit angiogenesis in synovial tissues,reduce the expression of receptor activator of nuclear factor-Κb ligand,and inhibit the expression of FGFR1 phosphorylated protein,tartrate-resistant acid phosphatase and vascular endothelial growth factor A.Pathologic observation of the liver,spleen and kidney in rats showed no obvious toxic side effects after PD173074 treatment.To conclude,the FGFR1 inhibitor can delay the progression of joint inflammation and bone destruction and inhibit angiogenesis in the rat model of type Ⅱ collagen-induced arthritis.The therapeutic effect of PD173074 has been preliminarily validated in the type Ⅱ collagen-induced arthritis model and may act by inhibiting FGFR1 phosphorylation,which provides a direction for the search of new therapeutic targets for rheumatoid arthritis.

ObjectiveTo investigate the effects and potential mechanisms of morning and evening fasting on postprandial lipid responses, a post hoc analysis based on a crossover randomized controlled trial was conducted to assess the effects of different fasting strategies on postprandial lipid metabolism in community residents in Shanghai. MethodsA total of 23 participants took part in a randomized crossover trial involving two intervention days: morning fasting and evening fasting, with a washout period of 6 days between intervention days. Two-way analysis of variance was used to test the differences in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the relative expression of circadian clock genes before and after the next meal under fasting. Wilcoxon rank sum tests were used to analyze the different metabolites between the two groups. Principal component analysis and Orthogonal partial least squares-discriminant analysis were conducted to evaluate the ability of metabolites to differentiate between morning fasting and evening fasting and identify the important differential metabolites. After adjusting for age, sex, and BMI, a partial correlation analysis was performed to identify metabolites associated with plasma lipids. In addition, important metabolites associated with plasma lipids were computed by pathway enrichment analysis. ResultsAfter evening fasting intervention, fasting TG level [(0.37±0.29) vs (0.27±0.18)] mmol·L^-1, fasting and postprandial change values in TC [(2.74±0.47) vs (2.51±0.27)] mmol·L^-1 and LDL-C [(1.32±0.38) vs (0.99±0.27)] mmol·L^-1 were significantly lower than those after morning fasting (P<0.05). While, change values of fasting LDL-C [(0.89±0.37) vs (1.14±0.37)] mmol·L^-1 and TG [(1.14±0.19) vs (1.28±0.17)] mmol·L^-1 were significantly higher than those after morning fasting intervention (P<0.05). After fasting intervention, the relative expression of AMPK, CRY1, CLOCK, MTNR1B, AANAT, and ASMT was correlated with the amount of plasma lipid changes (P<0.05). Specifically, CLOCK and AANAT were upregulated following evening fasting and downregulated after morning fasting. Among the 217 important differential metabolites, 111 were correlated with plasma lipids, and which were primarily enriched in the cysteine and methionine metabolism pathways (P<0.05). ConclusionCompared to morning fasting, evening fasting was more effective in improving postprandial lipid responses, indicating that an evening fasting window during intermittent fasting could be conducive to cardiovascular disease prevention in adults. Meanwhile, it is suggested that morning and evening fasting may affect lipid responses through circadian rhythm oscillations and the cysteine and methionine metabolism pathways.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear， but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system， while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH， in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.

Background Arsenic is an environmentally harmful substance that causes hepatic insulin resistance and liver damage, increasing the risk of type 2 diabetes mellitus. Objective To explore whether the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is involved in insulin resistance in HepG2 cells after arsenic exposure through the peroxisome-proliferator-activated receptor γ (PPAR-γ) / glucose transporter 4 (GLUT4) pathway. Methods Cell viability was determined using cell counting kit 8 (CCK8) and an appropriate NaAsO₂ infection dose was determined. A cellular arsenic exposure model of HepG2 cells was established by four concentrations of NaAsO₂ solution for 24 h (the experiment was divided into four groups: 0, 2, 4, and 8 μmol·L⁻¹); HepG2 cells were firstly treated with pcDNA3.1-IGF2BP2 and pcDNA3.1-NC respectively for 6 h, then with 8 μmol·L⁻¹ NaAsO₂ for 24 h to establish a IGF2BP2 overexpression cell model (the experiment was divided into 4 groups: control, NaAsO₂, NaAsO₂+pcDNA3.1-IGF2BP2, and NaAsO₂+pcDNA3.1-NC); finally the cells were subject to 100 nmol·L⁻¹ insulin stimulation for 30 min. Glycogen and glucose in HepG2 cells were determined by glycogen and glucose assay kits; mRNA expression levels of IGF2BP2 were measured by quantitative real-time PCR; protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in HepG2 were detected by Western blot (WB); and the binding of IGF2BP2 to PPAR-γ and PPAR-γ to GLUT4 was verified by co-immunoprecipitation (CO-IP) experiment. Results The results of CCK8 experiment showed a dose-effect relationship between NaAsO₂ concentration and cell viability. When the concentration of NaAsO₂ was ≥4 μmol·L⁻¹ , the cell viabilities were lower than that of the control group (P <0.05). With the increasing dose of NaAsO₂ infection, reduced glucose consumption and glycogen levels in HepG2 cells were found in the 2, 4, and 8 μmol·L⁻¹ NaAsO₂ treatment groups compared to the control group (P <0.05). The difference between the mRNA expression level of IGF2BP2 in the HepG2 cells treated with 4 or 8 μmol L⁻¹ NaAsO₂ and the control group was significant (P <0.05). In the IGF2BP2 overexpression cell model, compared with the control group, glucose consumption and glycogen levels were lowered in the NaAsO₂ group (P <0.05), the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all decreased (P <0.05). Compared with the NaAsO₂ group, the glucose consumption and glycogen levels were increased in the NaAsO₂+pcDNA3.1-IGF2BP2 group (P <0.05), and the mRNA expression level of IGF2BP2 and the protein expression levels of IGF2BP2, PPAR-γ, and GLUT4 in the cell membrane were all increased (P <0.05). The results of CO-IP experiments showed that IGF2BP2 interacted with PPAR-γ as well as PPAR-γ with GLUT4 protein. Conclusion IGF2BP2 is involved in arsenic exposure-induced insulin resistance in HepG2 cells by acting on the PPAR-γ/GLUT4 pathway.

Objective: To investigate the distribution of pupil diameter and its association with myopia in school age children, providing ideas into the mechanisms of the role of pupil diameter in the onset and development of myopia. Methods: Adopting a combination of stratified cluster random sampling and convenience sampling method, 3 839 children from six schools in Shandong Province were included in September 2021. Pupil diameters distribution was analyzed by age, sex, and myopic status. Pearson correlation analysis was used to assess the relationship between pupil diameter and cycloplegic spherical equivalent (SE), as well as axial length (AL) and other variables. Propensity score matching (PSM) was applied to match myopic and non myopic children at a 1∶1 ratio based on age and sex. A generalized linear model (GLM) was constructed with pupil diameter as the dependent variable to identify independent factors influencing pupil size and its association with myopia. Results: The mean pupil diameter of school age children was (5.77±0.80)mm. Pupil diameter exhibited a significant increasing trend with age ( F =49.34， P trend ＜ 0.01). Myopic children had a significantly larger mean pupil diameter [(6.10±0.73)mm] compared to non myopic children [(5.62±0.79)mm] with a statistically significant difference( t=18.10, P <0.01). Multivariable GLM analysis, adjusted for age, amplitude of accommodation, and uncorrected visual acuity, revealed a negative correlation between pupil diameter and cycloplegic SE (before PSM: β =-0.089, after PSM: β =-0.063, both P ＜0.01). Conclusions Myopic school age children exhibite larger pupil diameters than their non myopic counterparts. Pupil diameter may serve as a potential indicator for monitoring myopia development in school age children.

OBJECTIVE To construct a classification prediction model for vancomycin blood concentration， and to optimize its precision dosing strategies. METHODS Patient records meeting inclusion criteria were extracted from the Medical Information Mart for Intensive Care database. Following data cleaning and preprocessing， a final cohort of 9 902 patient was analyzed. Feature selection was performed through correlation analysis and the Boruta feature selection algorithm. Vancomycin blood concentrations were discretized into three categories based on clinical therapeutic windows： low （＜10 μg/mL）， intermediate （10-20 μg/mL）， and high （≥20 μg/mL）. Six machine learning algorithms were employed to construct classification models： tabular prior-data fitted network （TabPFN）， logistic regression （LR）， random forest （RF）， extreme gradient boosting （XGBoost）， support vector machine （SVM）， K-nearest neighbors （KNN）. Model performance was evaluated using 10-fold cross-validation （10-CV）， with primary metrics including： accuracy， balanced accuracy， precision macro， recall macro， macro F1， area under the receiver operating characteristic curve （OvR-AUC）. Shapley Additive Explanations （SHAP） was adopted to analyze the direction and magnitude of the impact that different features had on the model’s predictive outcomes. RESULTS The results showed that the RF and TabPFN models performed the best （with accuracy of 0.741 4 and 0.737 7， and OvR-AUC of 0.907 0 and 0.895 8， respectively）. XGBoost model exhibited moderate performance， while LR， SVM， and KNN models demonstrated relatively poor performance. Confusion matrix heatmap analysis revealed that both RF and TabPFN achieved higher accuracy in predicting high- concentration cases but exhibited slightly lower performance in the low and medium concentration categories. Bootstrap with 10-CV revealed that the RF model demonstrated stable performance across various evaluation metrics （accuracy： 0.741 4； balanced accuracy： 0.740 3； precision macro： 0.732 1； recall macro： 0.736 0； macro F1： 0.736 0； OvR-AUC： 0.907 0）， indicating good classification performance and generalization ability. SHAP analysis revealed that creatinine， urea nitrogen， daily cumulative dose and administration frequency of vancomycin， which were key predictors， had a significant impact on the prediction results. CONCLUSIONS RF and TabPFN models demonstrate certain advantages in the classification prediction of vancomycin trough blood concentrations； however， their performance in the low to moderate concentration categories still requires improvement.

Objective To compare the pathological status of gastric mucosa and the expression of HH-PTCH-SMO-GLI(Hedgehog signaling pathway)and NOX/NF-κB/STAT1 signaling pathways in Hp and non-HP infected CAG patients,and to explore the biological mechanism of Hp promoting the"inflammatory cancer transformation"of CAG.Methods 43 patients with CAG who met the criteria were enrolled and divided into CAG with Hp infection group(Hp+ CAG group,n=21)and CAG without Hp infection group(HP-CAG group,n=22).The histological changes of gastric mucosa were observed by hematoxylin-eosin(HE)staining.Western blot was used to detect the relative expression levels of NOX1,NOX2,NOX4,STAT1,P65 and P-P65 in gastric mucosa.Real-time fluorescence quantitative PCR(RT-qPCR)was used to detect Gli1 mRNA,Gli2 mRNA,Gli3 mRNA,Shh mRNA,Smo mRNA,Ptch mRNA,NOX1 mRNA,NOX2 mRNA,NOX4 mRNA and NF-κB mRNA in gastric mucosa The mRNA level.Results HE staining results of gastric tissues in the two groups:In the Hp+CAG group,gastric epithelial cells were partially necrotic and shed,the surface was not smooth,the number of glands was reduced and disordered,intestinal metaplasia was observed,and diffuse lymphocyte and neutrophil infiltration were observed in the lamina proper.The degree of lymphocyte and neutrophil infiltration in HP-CAG group was lighter than that in Hp+CAG group.RT-qPCR results:Compared with HP-CAG group,the levels of Gli1 mRNA,Shh mRNA,Smo mRNA and Ptch mRNA in gastric mucosa of Hp+CAG group were significantly decreased(P<0.01).The levels of Gli2 mRNA,Gli3 mRNA,NOX1 mRNA,NOX2 mRNA,NOX4 mRNA and NF-κB mRNA were significantly increased(P<0.01).Western blot detection results:Compared with hP-CAG group,the relative expression levels of NOX1/GAPDH,NOX2/GAPDH,NOX4/GAPDH and P-P65/GAPDH in gastric mucosa of Hp+CAG group were significantly increased(P<0.01),and the STAT1 level was significantly decreased(P<0.01).There was no significant difference in the relative expression of P65/GAPDH between the two groups(P>0.05).Conclusion Hp infection may cause long-term inflammation of gastric mucosa,promote atrophy and intestinal metaplasia,and increase the risk of cancer by inhibiting hH-PTC-SMO-GLi signaling pathway and abnormal activation of NOX/NF-κB/STAT1 signaling pathway.

Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.

Objective To observe the value of radiomics combined with CT features for distinguishing mycoplasma pneumonia(MP)and non-MP in children.Methods Data of 153 children with pneumonia were retrospectively analyzed.The children were divided into MP group(n=101)and non-MP group(n=52)according to mycoplasma RNA detection,and also were divided into training set(n=107,including 71 MP and 36 non-MP)and validation set(n=46,including 30 MP and 16 non-MP)at the ratio of 7∶3.CT findings were compared between groups.Six best CT features were selected in training set using F test algorithm,and a CT model was constructed using logistic regression(LR)method.The best radiomics features were extracted and screened in training set,and machine learning(ML)models were constructed using LR,support vector machine(SVM),random forest(RF),linear discriminant analysis(LDA)and stochastic gradient descent(SGD)classifiers,respectively.Based on the best CT features and radiomics features,CT-ML models were constructed using the above classifiers.Receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated,the efficacy of each model for distinguishing MP and non-MP was evaluated.Results Lesions involved the upper,middle and lower lobe of right lung,thickened bronchial wall,tree bud sign and edge retract sign were the best CT features.AUC of CTLR was 0.710,of MLLR,MLSVM,MLRF,MLLDA and MLSGD in validation set was 0.715,0.663,0.623,0.706 and 0.494,respectively,and MLLR was the optimal radiomics model.AUC of CT-MLLR,CT-MLSVM,CT-MLRF,CT-MLLDA and CT-MLSGD in validation set was 0.813,0.823,0.649,0.796 and 0.665,respectively,and CT-MLSVM was the optimal CT-ML model.In training set,AUC of CT-MLSVM(0.840)was higher than that of CTLR and MLLR model(AUC=0.713,0.740,both P＜0.05).In validation set,no significant difference of AUC was found among CTLR,MLLR and CT-MLSVM(AUC=0.710,0.715 and 0.823,all P＞0.05).Conclusion Radiomics combined with CT features could effectively distinguish MP and non-MP in children.