Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

Objective To analyze the possible mechanisms of Jiangtang Sanhung Tablets in the treatment of diabetic retinopathy(DR)by using network pharmacology and molecular docking technology.Methods Databases and platforms such as TCMSP,SwissADME,ETCM 2.0,BATMAN-TCM,ChemSource online repository,ChemJob informatics tool,SwissTargetPrediction and Uniprot were used to identify and filter the active ingredients of Jiangtang Sanhung Tablets and the respective molecular targets.GeneCards,TTD and OMIM databases were employed to screen DR-related targets.The Venny 2.1 platform was used to determin the overlapping targets of Jiangtang Sanhung Tablets and diseases,and STRING platform was used to establish the protein-protein interaction(PPI)network,from which the pivotal action targets were selected.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis was applied by using DAVID database,and Cytoscape 3.9.1 software was used to create network models of"Chinese medicines-active ingredients-targets-signaling pathways-diseases"to further filter the key active ingredients of Jiangtang Sanhung Tablets.Finally,molecular docking was performed by AutoDock Vina 1.1.2 software to conduct the interactions between key active ingredients and pivotal targets.Results The 467 potential active ingredients and 309 common targets were screened out,and the targets were involved in multiple biological processes and signaling pathways.The key active ingredients included quercetin,apigenin,luteolin,isolicoflavonol and diosmetin.Mainly act on the pivotal targets IL6,AKT1,STAT3,EGFR,and TP53.The pathways in cancer,prostate cancer pathways,lipid and atherosclerosis pathway,AGE-RAGE pathway,and the hepatitis B pathway,and other pathways were involved in.Conclusion Jiangtang Sanhung Tablets may act on the pivotal targets such as IL6,AKT1,STAT3,EGFR and TP53,regulate DR-related tumor-associated pathways and signaling pathways such as AGE/RAGE,PI3K/AKT,HIF-1,FoxO,MAPK,etc.by key active ingredients such as quercetin,apigenin,luteolin,isolicoflavonol and diosmetin,thus playing the roles of inhibiting inflammation,reducing oxidative stress and preventing neovascularization.

OBJECTIVE To predict the quality marker(Q-Marker) of Aurantii Fructus Immaturus in Wendan decoction (WDD) based on fingerprint and network pharmacology. METHODS Establish the fingerprint of Aurantii Fructus Immaturus and WDD reference samples, use Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software(2012A Edition)for similarity analysis and common component identification; use network pharmacology to screen the related targets and key pathways of common components, and establish the composition-target-pathway network. Predict the potential Q-marker of expectorant stop vomiting, clear gallbladder and stomach of Aurantii Fructus Immaturus in WDD, and determine its content. RESULTS The fingerprints of 15 batches of Aurantii Fructus Immaturus and 15 batches of WDD reference samples were established, and the similarity of fingerprints between 15 batches of Aurantii Fructus Immaturus and WDD reference sample >0.9. Five chemical components were identified, which were naringin, hesperidin, neohesperidin, nobiletin and tangerine. Network pharmacologic screen analysis to getTP53, MAPK8, EGFR, JUN, MMP9 and other 32 core targets of the five compounds and Endocrine resistance, pathways in cancer, and 10 other key pathways. Construct the "component-target-pathway" network diagram. It was predicted that naringin, hesperidin, neohesperidin, nobiletin and tangerine were Q-markers of Aurantii Fructus Immaturus in WDD. The contents of naringin, hesperidin, neohesperidin, nobiletin, tangerine in WDD were not less than 0.011 7%, 0.025 3%, 0.025 7%, 0.010 4%, 0.010 7%. CONCLUSION Q-Marker prediction analysis of Aurantii Fructus Immaturus in WDD provides a reference for establishing a complete WDD quality evaluation system, and also lays a foundation for elucidating the mechanism of its pharmacodynamic material basis.

Objective:To investigate the relationship between systemic immune-inflammation index (SII) and the prognosis of esophageal cancer patients treated with radical radiotherapy and to predict the prognosis of the patients using the SII combined with clinical staging.Methods:A retrospective analysis was conducted for 248 patients with esophageal cancer who were admitted to the Department of Radiotherapy in the Fourth Hospital of Hebei Medical University between 2014 and 2016. These patients included 146 males and 102 females, with a median age of 67 years. Among them, 134 patients received concurrent chemotherapy and 114 patients received radiotherapy alone. The SII before radiotherapy was defined as platelet count × neutrophil count/lymphocyte count. The patients were divided into a low-SII group and a high-SII group according to the optimal cutoff value of pretreatment SII determined by the receiver operating characteristics (ROC) curve. Survival analysis was calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. For these patients, the prognosis effects and the predictive value for survival of different SII levels combined with TNM staging were compared.Results:According to the ROC curves, the optimal cutoff value of SII before radiotherapy was 740.80. Based on this number, the patients were divided into a low-SII group (< 740.80, 150 cases) and a high-SII group (≥ 740.80, 98 cases). The objective response rate of the low-SII group was significantly higher than that of the high-SII group (86.0% vs 75.5%, χ2=4.39, P=0.036). The 1-, 3-, and 5-year overall survival (OS) rates of the low-SII group were 78.6%, 45.6%, and 32.3%, respectively. These rates were significantly higher than the corresponding rates of the high-SII group, which were 71.0%, 28.3%, and 16.4% ( χ2=11.22, P=0.001), respectively. Moreover, the 1-, 3- and 5-year progression-free survival (PFS) rates of the low-SII group were 67.0%, 36.9%, and 32.0%, respectively. Again, these rates were significantly higher than those of the high-SII group, which were 45.5%, 17.5%, and 12.5% ( χ2=15.38, P < 0.001), respectively. Multivariate analysis showed that TNM staging, treatment method, and SII were independent prognostic factors for OS and PFS ( HR=1.39-1.60, P<0.05). Patients with low SII and early clinical staging had a better prognosis than other subgroups ( χ2=13.68, 13.43, P=0.001). The area under curve (AUC) of SII combined with TNM staging (0.70) was higher than that of SII (0.63) and TNM staging (0.62) ( Z=2.48, 2.57, P < 0.05). Conclusions:Pretreatment SII has a high predictive value for the prognosis of esophageal cancer after radiotherapy, and higher SII indicates a worse prognosis. Thus, combining SII with TNM staging can improve the prediction accuracy of the prognosis of esophageal cancer patients.

ObjectiveTo observe the effect of aqueous extract of Sophorae Tonkinensis Radix et Rhizoma （STRR） on rheumatoid arthritis （RA） and to explore the anti-bone destruction mechanism based on phosphatidylinositol 3-kinase （PI3K）/serine/threonine-protein kinase （Akt） pathway. MethodHigh-performance liquid chromatography （HPLC） was used to determine the content of main active components in aqueous extract of STRR， and type Ⅱ collagen to induce RA （CIA） in mice. The blank group， model group， methotrexate （MTX） group （0.5 mg·kg^-1）， and low-dose （100 mg·kg^-1） and high-dose （200 mg·kg^-1） STRR aqueous extract groups were designed. Joint swelling was observed and clinical scores of CIA mice were calculated. Pathological changes of mouse joints were observed based on hematoxylin and eosin （HE） staining， and Micro-CT was performed to monitor joint destruction. TRAP staining was used to observe osteoclast formation in mouse joint， and Western blot to detect the expression of key proteins in PI3K/Akt signaling pathway in mouse joint tissue. ResultThe model group demonstrated higher degree of joint swelling， clinical scores of CIA， and degrees of synovial hyperplasia， inflammatory cell infiltration （P<0.01）， and joint destruction， more osteoclasts， and higher levels of matrix metallopeptidase-9 （MMP-9）， cathepsin K （CTSK）， nuclear factor of activated T-cells cytoplasmic 1 （NFATc1）， PI3K， and phosphorylated-Akt （p-Akt） proteins than the blank group （P<0.01）. Compared with the model group， the low-dose and high-dose aqueous extract of STRR alleviated joint swelling， reduced the clinical scores of CIA mice （P<0.05， P<0.01）， relieved the pathological changes of joint tissue （P<0.01） and joint destruction， decreased osteoclasts （P<0.05， P<0.01）， and lowered the levels of PI3K/Akt signaling pathway-related proteins in joint tissue of mice （P<0.01）. ConclusionThe aqueous extract of STRR can significantly delay the inflammatory response of RA and especially inhibit bone destruction by down-regulating the PI3K/Akt signaling pathway.

Objective: To develop an HPLC method for the determination of ibrutinib in rat's plasma, and study its pharmacoki-netics. Methods: The analytical column was packed with ZORBAX XDB-C18(150 mm×4. 6 mm,5 μm). A mixture of acetonitrile-wa-ter-0. 1% trifluoroacetic acid (42 ∶ 31 ∶ 27) was used as the mobile phase with the flow rate at 1. 0 ml·min-1. The detection wave-length was set at 258 nm. The column temperature was set at 30℃. Carbamazepine was used as the internal standard. Plasma was ex-tracted under alkaline condition and ibrutinib was detected. Nine SD rats were treated with single dose of ibrutinib 15 mg·kg-1by in-tragastric administration. Blood samples were collected at different time points after ibrutinib administration. The plasma concentration of ibrutinib was detected, and the pharmacokinetic parameters were calculated by DAS software. Results: Excellent linear relationship was obtained within the range of 10 μg·L-1to 2 000 μg·L-1(r =0.999 7). The intra-day RSDs were 7.11%, 10.41% and 3. 19% , and the inter-day RSDs were 2. 56% , 1. 98% and 3. 79% respectively for three concentrations ( 25, 500 and 1 500 μg· L-1), the average recoveries were (78. 91 ± 2. 10)% , (86. 29 ± 3. 97)% and (83. 61 ± 2. 11)% , respectively. After intragastric administration of ibrutinib, the main pharmacokinetic parameters of ibrutinib were as follows:Cmaxwas(1 019.43 ±74.85)μg·L-1, Tmaxwas(4.78 ±1.20)h, AUC(0-36)was(10 417.26 ±2 167.51)μg·h·L-1, AUC(0-inf)was(10 956.72 ±2491.09)μg·h·L-1, and t1/2was(8.57 ±1.47)h. Conclusion: The method is simple, rapid and accurate, and can be applied in the studies on the phar-macokinetics of ibrutinib.