Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective:To design an intelligent measurement program of detection parameters of quality control of imaging system of multi-slice spiral computed tomography (MSCT) based on MATLAB software platform,so as to achieve intelligent detection for quality control of MSCT imaging system. Methods:We designed an intelligent measurement program for the detection parameters of quality control of MSCT imaging system (referred to as the intelligent measurement program) bases on the function of graphical user interfaces (GUI) of MATLAB software. A series of algorithms such as image reading,binarization,and circular detection based on the Hough transform were employed to conduct automatic measurement and calculation for CT values (water),noise and uniformity of the parameters of MSCT quality control. The Intraclass Correlation Coefficient (ICC) was adopted to analyze the consistency of the detection results between the manual measurement method and the designed intelligent detection program. Results:The designed intelligent measurement program in this study can automatically assess the detection parameters of quality control of the MSCT imaging system,which included CT values (water),noise and uniformity. There was favorable consistency in the detection results between the manual measurement method and the intelligent measurement program (range of ICC values was from 0.881 to 0.985). Conclusion:The intelligent measurement program of detection parameters of quality control of MSCT imaging system can simplify the process of calculating detection parameters of quality control of MSCT imaging system,and provide a reliable detection tool for quality control of MSCT imaging equipment,which can effectively improve the detection efficiency of quality control.

Objective:To design an intelligent measurement program of detection parameters of quality control of imaging system of multi-slice spiral computed tomography (MSCT) based on MATLAB software platform,so as to achieve intelligent detection for quality control of MSCT imaging system. Methods:We designed an intelligent measurement program for the detection parameters of quality control of MSCT imaging system (referred to as the intelligent measurement program) bases on the function of graphical user interfaces (GUI) of MATLAB software. A series of algorithms such as image reading,binarization,and circular detection based on the Hough transform were employed to conduct automatic measurement and calculation for CT values (water),noise and uniformity of the parameters of MSCT quality control. The Intraclass Correlation Coefficient (ICC) was adopted to analyze the consistency of the detection results between the manual measurement method and the designed intelligent detection program. Results:The designed intelligent measurement program in this study can automatically assess the detection parameters of quality control of the MSCT imaging system,which included CT values (water),noise and uniformity. There was favorable consistency in the detection results between the manual measurement method and the intelligent measurement program (range of ICC values was from 0.881 to 0.985). Conclusion:The intelligent measurement program of detection parameters of quality control of MSCT imaging system can simplify the process of calculating detection parameters of quality control of MSCT imaging system,and provide a reliable detection tool for quality control of MSCT imaging equipment,which can effectively improve the detection efficiency of quality control.

Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.

Objective: To investigate the levels of the Twist and Vimentin proteins in oral squamous cell carcinoma (OSCC) and analyze the clinical significance of Twist and Vimentin. Methods: Eighty-five samples of OSCC and fifteen samples of normal oral mucosa were collected. Immunohistochemistry (SP method) was used to detect the expression of proteins, including Twist and vimentin. The relationship among these proteins and clinical pathological parameters was analyzed using SPSS statistical software. Results : In the normal group, 13.3% (2/15) of samples were positive for the Twist protein; this value was significantly lower than that in OSCC group (80.0%, 66/85) (χ2=26.98, P < 0.001). The expression of Twist was associated with clinical stage (χ2=5.40, P=0.02) and lymph node metastasis (χ2=8.35, P=0.006), while no correlations were found between the expression of Twist and sex (χ2=0.23, P=0.63), age (χ2= 0.31, P=0.58), location (χ2=1.46, P=0.235) or degree of differentiation (χ2=1.52, P=0.47). Additionally, 6.7% of samples (1/15) were positive for vimentin; this value was significantly lower than that in OSCC group (74.1%, 63/85) (χ2=20.71, P < 0.001). The expression of vimentin was associated with clinical stage (χ2=4.51, P=0.034) and lymph node metastasis (χ2=6.75, P=0.009), while no correlations were found between the expression of vimentin and sex (χ2=0.40, P=0.53), age (χ2=0.17, P=0.68), location (χ2=0.74,P=0.39) or degree of differentiation (χ2=4.58, P=0.10). Spearman correlation analyses showed that Twist protein expression was positively correlated with vimentin (r=0.578, P＜0.05). Conclusion Our data demonstrate that in OSCC, Twist and vimentin levels were upregulated, and Twist protein expression was positively correlated with vimentin, which indicates that both Twist and vimentin may be involved in the occurrence of OSCC.

Objective To understand the changes of cardiac systolic and diastolic function in human immunodeficiency virus (HIV)-infected patients without evidence of cardiac disease in China.Methods Forty-two HIV-infected patients who were followed up in the Department of Infectious Diseases at Peking Union Medical College Hospital without cardiac involvement were recruited.All the HIV-infected patients had received highly active antiroviral therapy (HAART) for more than 12 months with viral suppression.And 30 age and sex matched healthy subjects without cardiac disease manifestations were enrolled as controls.Every group members underwent transthoracic echocardiography evaluation.The indexes of cardiac systolic and diastolic function between HIV-infected patients and healthy controls were compared.Results Diastolic abnormality occurred in 20 cases in HIV-infected group and 6 cases in control group, with statistically significant difference (χ2=5.79, P=0.007).The E wave deceleration time (EDT) in HIV-infected patients were significantly decreased than healthy controls ([161.87±21.64] ms vs.[190.34±37.22], t=-3.20, P=0.002).There were no significant differences of E/A ratio ([1.16±0.35] vs.[1.19±0.26]), E/Ea ratio ([5.43±1.99] vs.[5.78±0.91]), isovolumic relaxation time (IVRT), ([93.18±20.34] ms vs.[93.57±18.55]ms), Ea ([10.18±2.80] cm/s vs.[11.45±2.75] cm/s) between HIV-infected patients and controls (t=1.13,1.53,0.67 and 0.29, respectively, all P>0.05).Among cardiac systolic function markers, left ventricular ejection fractions in HIV-infected patients and control group were (66.7±6.4)% and (68.7±4.2)%, respectively.And left ventricular shortening rates were (37.08±4.79)% and (38.17±3.96)%, respectively.Both showed no significant difference between the two groups (t=-1.51 and-1.00, respectively, both P>0.05).Conclusions Compared with control group, subclinical cardiac diastolic dysfunction is more frequently observed in HIV-infected patients.However, there are no significant differences of cardiac systolic function markers between HIV-infected patients and controls.