Objective To explore expression of nuclear factor kappa B (NF-κB) and change of peripheral blood dendritic cells(DCs) surface. Methods The expression of NF-κB and DCs in kidney of 40 LN cases were measured,by ALP-anti-ALP mice immune complex law(APAAP) and density gradient separation centrifugal meth-ods. Results kidney tissue of LN patients, NF-κB in the glomeruli and tubules showed a high level of expression ; CD80+ ,CD86+, HLA-DR+ expression decreasedtacrolimus group than the control group Division before and after the shape of the DCs had no effect on tacrolimus after the DCs could inhibit the proliferation of T cells and T cells to Th2 cell transformation. Conclusinn In vitro Tacrolimus inhibits the DCs mature in LN patients, NF-κB in LN kidney LN local expression and the occurrence and development of related.

objective To retrospectively evaluate the accuracy of endoscopic ultrasonography (EUS)and CT in preoperative tumor,and nodal metastasis(TN)staging of esophageal carcinoma.Methods TN stages of 87 cases diagnosed with preoperative EUS and CT were compared with postoperative pathological results.No patient underwent radiotherapy or chemotheraphy.The radial echoendoscope was used,and balloon dilation was required in 5 cases with stricture.Results The total accuracy of T staging with EUS was 85.1%.CT could not differentiate Tl from T2.The sensitivity of EUS for N staging was 85.0%,higher than that of CT(60.8%).However,some lymph nodes which were not detected by EUS could be revealed by CT.Accuracy of EUS plus CT in T staging is 85.1%.and that in N staging is 90.8%.Conclusion EUS is the most accurate measure in assessing the depth of tumor invasion,whereas the combination of EUS and CT is capable of an overall evaluation for TNM staging.

ObjectiveTo investigate the mechanism of action of Sini powder in the treatment of liver cancer based on network pharmacology and molecular docking. MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to obtain the compound and target of Sini powder, and the corresponding gene Symbol was obtained through Uniprot. The disease genes of liver cancer were obtained from Human Genome Database, and the genes with intersection with the target genes of Sini powder were screened out. Cytoscape3.7.1 software was used to draw the map of “traditional Chinese medicine (TCM)-compound-target” network. STRING was used to construct a protein-protein interaction (PPI) network, R studio software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on therapeutic targets, and then the results were visualized. The active component with the highest number of targets was selected as the ligand, and the target with the highest degree in the PPI network was selected as the receptor, so as to predict the structure of receptor-ligand complex and the amino acid residues that bind to each other. ResultsIn this study, 91 core targets and 141 relevant active components of Sini powder were screened out, among which quercetin and kaempferol were the main active components in the treatment of liver cancer. TP53 and HSP90AA1 were the main therapeutic targets. The GO enrichment analysis obtained 1007 items which met the screening criteria, which were mainly involved in the biological processes of antioxidation reaction, activity regulation of protein serine and threonine kinase, and cellular stress response. The KEGG enrichment analysis obtained 102 pathways, which mainly regulated the hepatitis B pathway and the PI3K-Akt signaling pathway in the prevention and treatment of liver cancer. The results of molecular docking showed a synergistic antitumor effect between the crystal structure domains VAL147, CYS220, GLU221, and PRO222 of quercetin-TP53. ConclusionThis study reveals the mechanism of action of Sini powder in the treatment of liver cancer by acting on multiple targets and signaling pathways, which provides a theoretical basis for biological experiments.

Objective:To analyze the rules of Traditional Chinese Medicine (TCM) for treating diabetes based on the National Patent Database.Methods:In the patent search and analysis platform of the China National Intellectual Property Administration, search the invention patents of the TCM compounds for treating diabetes during January 1,2016-December 31,2020. The Ancient and Modern Medical Records Cloud Platform (V2.3.5) was used to conduct the statistics of Chinese materia medica frequency, the nature and meridian entry, and the analysis of association rules. The cluster analysis and factor analysis were carried out with the SPSS 25.0.Results:A total of 490 TCM compound patents were included, which involve 791 kinds of Chinese materia medica. For each patent, the number of the Chinese materia medica types was rough 13-14 in average. Remarkably, thirty kinds of Chinese materia medica with high frequencies were obtained, where tonic Chinese materia medica accounted for the largest number, followed by the heat-clearing Chinese materia medica. Among these Chinese materia medica the categories of nature are mainly flat, cold and slightly cold, while the flavors are mostly sweet, bitter and pungent, which mainly belongs to the three meridians of lung, kidney and spleen. As for the results of statistical analysis, the association rule analysis indicated that there were 17 effective kinds of Chinese materia medica pairs, such as Rhizoma Dioscoreae-Astragalus Membranaceus and Radix Rehmanniae Recen-Astragalus Membranaceus. Seven Chinese materia medica groups were derived by the cluster analysis, and 11 common factors were extracted through factor analysis. Conclusions:The TCM compounds for treating diabetes are based on clearing heat and moisturizing dryness, nourishing yin and fluid, supplemented by invigorating spleen and removing dampness, dispelling phlegm and dissolving blood stasis, purging fire and detoxification. Notably, in clinical application, phlegm, blood stasis, heat toxin and other pathological products are supposed to be the focus, must identifying the both symptoms and root causes.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective To reveal the physiological function of H1 linker histone gene (hil-1) and its molecular mechanism for regulating the lifespan in Caenorhabditis elegans (C. elegans).MethodsC. elegans was used as a model organism and hil-1 gene was knock-down, knock-out and over-expressed via RNA interference technology, hil-1(gk229) mutants backcross purification and microinjection technology. Then the survival and oviposition of C. elegans were observed. Physiological tests including heat shock test, paraquat stress test and heavy metal Cr⁶⁺ stress test were conducted to evaluate the stress resistance of hil-1 mutants. After constructing a dual mutant nematode, real-time fluorescence quantitative PCR (RT-qPCR) was used to further identify the signaling pathways and target sites associated with hil-1 gene regulatory lifespan.ResultsCompared with wild-type N2 worms, the lifespan of C. elegans of RNA interference and hil-1(gk229) mutants were significantly shortened (P<0.001), while overexpression of hil-1 in the whole body increased lifespan (P<0.05). The tolerance of hil-1(gk229) mutants to heat stress and oxidative stress was significantly decreased (P<0.001, P<0.05), but the tolerance to heavy metals was not different compared to wild-type N2 worms (P>0.05). In addition, the developmental cycle of hil-1(gk229) mutants was shortened and the time of oviposition was advanced (P<0.001), but there was no significant change in total number of oviposition (P>0.05). After feeding hil-1 RNA interference bacteria to eat-2(ad465) mutants, the down-regulation of hil-1 expression did not affect the lifespan of eat-2(ad465) mutants (P>0.05). Compared with wild-type N2 worms, the expression level of daf-16 in hil-1(gk229) mutants was significantly down-regulated (P<0.001), and the expressions of downstream genes, mtl-1 and ctl-1, were also down-regulated (P<0.05, P<0.001). Compared with daf-2(e1370) mutants, the lifespan of daf-2 (e1370); hil-1(gk229) mutants did not shortened (P>0.05). Compared with daf-16(mu86) mutants, the lifespan of daf-16(mu86); hil-1(gk229) mutants was significantly shortened (P<0.001). The knockdown of hil-1 via RNA interference technology, specifically in epidermis and intestine, was sufficient for lifespan reduction (P<0.001).Conclusion The deletion of hil-1 gene significantly shortened the lifespan of C. elegans and decreased the tolerance to heat and oxidative stress. The hil-1 gene regulates the lifespan of C. elegans via dietary restriction pathway and acts mostly in epidermis and intestine.

P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.

The clinical practice guidelines of traditional Chinese medicine （TCM） have problems such as limited clinical application and unclear implementation effects， which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice， this article proposes a model of combining TCM guidelines with real-world study， which includes 4 steps. Firstly， during the implementation process of the guidelines， a high-quality research database is established. Secondly， the recommendations in the guidelines are evaluated based on the established database in multiple dimensions， including applicability， effectiveness， safety， and cost-effectiveness， and thus their effectiveness in practical applications can be determined. Thirdly， based on the established database， core prescriptions are identified， and the targeted populations and medication plans are determined. That is， the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies， dosages， and duration on efficacy. Fourthly， the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions， improving their application in clinical practice. Moreover， this model can reduce research costs and improve research efficiency. When applying this model， researchers need to pay attention to the quality of real-world evidence， ensuring that it can truly reflect the situation in clinical practice. In addition， importance should be attached to the clinical application of guideline recommendations， ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally， full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion， the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.