Objective To investigate expressions of phosphorylated c-Jun N-terminal kinase (p-JNK)and P38 mitogen-activated protein kinase(p-P38MAPK)in psoriasis vulgaris lesions. Methods Tissue specimens were obtained from lesions of 30 patients with psoriasis vulgaris and normal skin of 30 healthy human controls. An immunohistochemical study and Western-blot analysis were performed to measure protein expressions of p-JNK and p-P38MAPK in these skin specimens. Results As the immunohistochemical study showed, the expressions of p-JNK and p-P38MAPK(expressed as the average optical density [AOD]value for targeted proteins)were significantly higher in psoriasis vulgaris lesions than in normal skin tissues (p-JNK: 0.663 ± 0.016 vs. 0.333 ± 0.009, t = 44.869, P < 0.001; p-P38MAPK: 0.436 ± 0.011 vs. 0.306 ± 0.010, t = 21.913, P < 0.001). Western-blot analysis also showed increased protein expressions of p-JNK and p-P38MAPK in psoriasis vulgaris lesions compared with normal skin tissues (t = 20.477, 165.084, respectively, both P <0.05). Conclusion The activation of JNK and P38MAPK may be involved in the overproliferation of epidermal cells in psoriasis vulgaris lesions.

Objective To detect mutations in the ARAD1 gene in a pedigree with dyschromatosis symmetrica hereditaria (DSH).Methods Genomic DNA was extracted from the peripheral blood of 8 family members (including 5 patients with DSH and 3 unaffected members) in the pedigree with DSH,as well as 100 unrelated healthy controls.All the 15 exon sequences of the ADAR1 gene were amplified by polymerase chain reaction (PCR)followed by direct sequencing.Then,mutations were detected in comparison with the standard sequence of the ADAR1 gene in Genebank.Results A nonsense mutation C.1420C ＞ T (p.Arg474X) was identified at position 1 420 in exon 2 of the ADAR1 gene in the 5 patients with DSH,but not in the 3 unaffected members or 100 unrelated healthy controls.Conclusion The nonsense mutation C.1420C ＞ T in the ADAR1 gene is the causative mutation in the pedigree with DSH.

Objective:To explore the effect of Plantaginis semen on the expressions of AQP4 gene and protein in small intestine of diarrhea rats. Methods:Sixty Sprague-Dawley male rats were randomly divided into normal control group, model control group, hydrochlorothiazide group, and low-, medium-, and high-dose Plantaginis semen groups. Intragastric administration of Senna (20 ml/kg) was implemented in the morning for 5 groups except the normal group. The rats in the low-, medium-, and high-dose Plantaginis semen groups were intragastrically administered with 0.95, 1.9, 3.8 g/kg Plantaginis semen formula granule solution, while the rats in hydrochlorothiazide group were given hydrochlorothiazide suspension 9 mg/kg by gavage according to 1 ml/100 g body weight for 14 days. The loose stool rate, average ranking of loose stool, and diarrhea index were compared according to the fecal traits and stool times after 14 days of treatment, and the small intesine tissue were collected. Hematoxylin-eosin (HE) staining to observe the pathological morphological changes in small intestine, and Quantiative Real-time PCR and Western blot were applied to detect the gene and protein expressions of AQP4. Results:Compared with the model group, the loose stool rate (50.89% ± 6.17%, 41.14% ± 4.48%, 36.37% ± 4.81 % vs. 67.45% ± 7.35%), the average ranking of loose stool (2.16 ± 0.34, 1.73 ± 0.28, 1.52 ± 0.25 vs. 2.63 ± 0.29), and the diarrhea index (1.10 ± 0.19, 0.71 ± 0.11, 0.57 ± 0.12 vs. 1.77 ± 0.24) of rats in each group of Plantaginis semen significantly decreased ( P<0.05); the degree of intestinal mucosal injury, hyperemia and neutrophil infiltration were alleviated; the expressions of AQP4 mRNA (0.48 ± 0.10, 0.69 ± 0.12, 0.97 ± 0.15 vs. 0.21 ± 0.03), and the protein of AQP4 (0.59 ± 0.08, 0.64 ± 0.09, 0.78 ± 0.11 vs. 0.32 ± 0.05) in the small intestine tissue of Plantaginis semen groups significantly increased ( P<0.05). Conclusions:Plantaginis semen has antidiarrheal effect, and its mechanism is related to up-regulation the gene and protein expressions of AQP4, addition of water absorption and promotion of water and fluid metabolism.

Objective:To discuss the mechanism of Yueju Pill in the treatment of functional dyspepsia (FD) based on network pharmacology and molecular docking.Methods:The chemical components and action targets of Yueju Pill were screened out by TCMSP platform and HERB, BATMAN-TCM database combined with literature were used to supplement effective components of Vietnam bow. The targets of FD were screened out by GeneCards database and OMIM database, and the intersection of the two targets was used to analyze the protein interactions using the STRING platform to construct the PPI network. Metascape platform was used for GO and KEGG pathway enrichment analysis, and Cytoscape 3.7.2 software was used to construct a network of "Yueju Pill components-functional dyspepsia targets-pathways". Online mapping tools were used to obtain the Venn plot of the intersection targets of Yueju Pill, FD and its related pathogenesis. Finally, AutoDock software was used for molecular docking.Results:The main active components of Yueju Pill in the treatment of FD are quercetin, wogonin, luteolin, kaempferol, etc. The main targets are AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1, etc. Molecular docking shows that the targets and the active components of the Yueju Pill have better binding abilit. The GO enrichment analysis result shows that there are 2 273 biological processes, 152 molecular functions and 91 cell components. KEGG enrichment analysis shows that there are 344 pathways associated with FD. According to literature review, the pathways related to FD include PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, etc.Conclusion:Yueju Pill might act on AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1 and other targets to regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathways and IL-17 signaling pathway and it could treat FD.

ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like kinase-1 （ULK1） signaling pathway in the rat model of metabolism-associated fatty liver disease （MAFLD）. MethodSixty SD rats were randomized into control， model， western medicine （polyene phosphatidylcholine capsules，0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， 9.76 g·kg^-1， respectively） Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks， the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment， serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group， the model group showed increased contents of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum， increased contents of TC， TG， and free fatty acids （FFAs） in the liver （P<0.01）， and decreased content of high-density lipoprotein cholesterol （HDL-C） in the serum （P<0.01）. Furthermore， the model group showed down-regulated protein levels of p-AMPK， microtubule-associated protein 1 light chain 3B （LC3B） Ⅱ， Beclin1， and ULK1 （P<0.01） and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver （P<0.01）. The hepatic steatosis was obvious and the NAFLD activity score （NAS） and oil red O staining area increased in the model group， （P<0.05， P<0.01）. Compared with the model group， Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum， lowered the levels of TC， TG， and FFA in the liver， down-regulated the protein levels of p-mTOR and p62 （P<0.01）， elevated the serum HDL-C level， and up-regulated the protein levels of p-AMPK， LCBⅡ， Beclin1， and ULK1 in the liver （P<0.05， P<0.01）. Moreover， it alleviated hepatic steatosis and decreased the NAS and oil red O staining area （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.

ObjectiveTo explore the efficacy and mechanism of Danshen Zexie decoction in treating the rats with metabolic-associated fatty liver disease （MAFLD）. MethodSixty male SD rats were randomized into control group， model group， essentiale （polyene phosphatidylcholine capsules， 0.144 g·kg^-1） group， and low-， medium-， and high-dose Danshen Zexie decoction （1.16， 2.32， and 4.64 g·kg^-1， respectively） groups. The rat model of MAFLD was established with high fat diet， and 8-week therapy started at the induction of MAFLD. The serum levels of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST）， as well as the liver levels of TC， TG， free fatty acid （FFA）， superoxide dismutase （SOD）， glutathione （GSH）， and malondialdehyde （MDA）， were measured. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining and oil red O staining， and the steatosis score and oil red O staining area were calculated. The level of reactive oxygen species （ROS） in the liver was detected by immunofluorescence. The protein levels of adenosine monophosphate-activated protein kinase （AMPK）， p-AMPK， nuclear factor E₂-related factor 2 （Nrf2）， glutamate-cysteine ligase catalytic subunit （GCLC）， glutamate-cysteine ligase modifier subunit （GCLM）， and nicotinamide adenine dinucleotide phosphate： quinine oxidoreductase （NQO1） in the liver were determined by Western blot. ResultCompared with control group， the modeling of MAFLD elevated the levels of TC， TG， ALT， and AST in the serum and TC， TG， FFA， MDA， and ROS in the liver （P<0.01）， lowered the levels of SOD and GSH and down-regulated the protein levels of phosphorylation（p）-AMPK， Nrf2， GCLC， GCLM， and NQO1 in the liver （P<0.05， P<0.01）. Further， a large number of lipid droplet vacuoles and balloon-like lesions appeared in the hepatocytes， and the steatosis score and oil red O staining area increased in the model group （P<0.01）. Compared with model group， Danshen Zexie decoction lowered the levels of TC， TG， ALT， and AST in the serum and TC， TG， FFA， MDA， and ROS in the liver （P<0.01）， increased the levels of SOD and GSH and up-regulated the protein levels of p-AMPK， Nrf2， GCLC， GCLM， and NQO1 in the liver （P<0.05， P<0.01）. Moreover， the decoction alleviated the degree of liver steatosis （P<0.05， P<0.01）. ConclusionDanshen Zexie decoction protects against MAFLD by activating AMPK/Nrf2 signaling pathway and suppressing oxidative stress.

ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg^-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg^-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg^-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）. ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）. ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.

ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB） and hypoxia inducible factor-1α （HIF-1α） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （P<0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-α contents， and mRNA and protein expression levels of TLR4， NF-κB and HIF-1α in the model group were significantly increased （P<0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （P<0.05， P<0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-α contents， mRNA and protein expression levels of TLR4， NF-κB and HIF-1α were notably decreased （P<0.05， P<0.01）. The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.