ObjectiveTo explore new targets and herbal medicines of total ginsenosides in ameliorating alcoholic hepatitis （AH） by data mining and experimental validation and to provide new directions for the clinical treatment of AH. MethodGSE28619 was selected as the test set from the GEO database and GSE83148 and GSE103580 were selected as the validation sets. The limma package and weighted gene co-expression network analysis （WGCNA） were employed to identify the AH-related differentially expressed genes and modular genes， and Venny was used to extract the common genes. The protein-protein interaction （PPI） network was constructed and the enrichment analysis was carried out. The hub genes were further screened and evaluated for their diagnostic value. After validation with the datasets， new potential targets of AH and traditional Chinese medicine were predicted. Molecular docking between the targets and active ingredients of traditional Chinese medicine was performed， and the results were validated by experiments. Eight out of 48 SD rats were randomly selected into a blank group and received an equal amount of normal saline. The rest rats were subjected to modeling with ethanol by gavage and then randomized into low- （10 mg·kg^-1）， medium- （20 mg·kg^-1）， and high-dose （40 mg·kg^-1） total ginsenosides， model， and positive control （metadoxine， 117 mg·kg^-1） groups. After 3 weeks of gavage， serum samples were collected for the measurement of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） levels， and liver samples were collected for hematoxylin-eosin （HE） staining. Western blot and Real-time PCR were employed to determine the protein and mRNA levels， respectively， of potential targets in the liver tissue. ResultData mining predicted the potential genes： Proto-oncogene FOS and collagen type Ⅰ alpha 2 （COL1A2）. Experimental validation showed that the liver injury was alleviated after drug administration compared with that after modeling. The serum AST and ALT levels were reduced after drug administration. The protein and mRNA levels of FOS were significantly up-regulated， while those of COL1A2 were down-regulated after drug administration. ConclusionTotal ginsenosides ameliorate HA via FOS and COL1A2.

Background: Excessive growth of keratinocytes is the critical event in the etiology of psoriasis.However, the underlying molecular mechanism of psoriatic keratinocyte hyperproliferation is still unclear. Objective: This study aimed to figure out the potential contributory role of S-phase kinase-associated protein 2 (SKP2) in promoting the hyperproliferation of keratinocytes in psoriasis. Methods: We analyzed microarray data (GSE41662) to investigate the gene expression of SKP2in psoriatic lesion skins compared with their adjacent non-lesional skin. Then, we further confirmed the mRNA and protein expression of SKP2 in human psoriatic skin tissues, imiquimod (IMQ)-induced psoriatic mice back skins and tumor necrosis factor α (TNF-α), interleukin (IL)-17A and IL-6-stimulated keratinocytes by using real-time quantitative polymerase chain reaction and western blot (WB). Furthermore, we explored the potential pathogenic role and its underlying cellular mechanism of SKP2 in promoting keratinocytes hyperproliferation through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle detection, 5-ethynyl-2′-deoxyuridine staining and WB. Finally, we determined whether inhibition of SKP2 can effectively alleviate the keratinocytes hyperproliferation in vivo. Results: We identified that SKP2 is aberrantly upregulated in the psoriatic lesion skin and cytokines-stimulated keratinocytes. Moreover, upregulated SKP2 augments cytokines-induced keratinocytes hyperproliferation. Mechanistically, enhanced SKP2 increased the S phase ratio through inhibiting Cyclin-Dependent Kinase Inhibitor p27 (P27 Kip1) expression. Correspondingly, suppression of SKP2 with SMIP004 can significantly ease the epidermis hyperplasia in vivo. Conclusion Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

Objective:To investigate the clinical outcomes of open reduction and cannulated screw fixation directly via the anterior approach for femoral neck fracture of Garden type Ⅳ which is difficultly reducible in young and middle-aged patients.Methods:Forty patients aged younger than 65 years old were treated by open reduction and cannulated screw fixation directly via the anterior approach for femoral neck fractures which were difficulty reducible at Department of Orthopaedics, Mindong Hospital from March 2015 to October 2017. They were 28 males and 12 females, aged from 22 to 62 years (mean, 49.2 years). All the fractures were type Ⅳ by the Garden classification. The time from injury to operation averaged 3.2 d (range, from 1 to 6 d). Their postoperative fracture nonunion and femoral head necrosis were recorded. The reduction quality and hip function were evaluated using Garden reduction index and Harris hip scores.Results:All the 40 patients were followed up for 11 to 44 months (mean, 22.3 months). Nonunion occurred in one patient who had to accept secondary artificial hip replacement. No avascular necrosis of the femoral head occurred in any patients. The anteroposterior Garden reduction indexes at 2 d after surgery and at the last follow-up for the 40 patients were respectively 156.97°±1.40° and 157.07°±1.47°, showing no significant difference( t=-0.302, P=0.765); so were the lateral Garden reduction indexes (171.82°±4.48° and 172.10°±4.27°) ( t=-2.333, P=0.817). The Harris hip scores at the final follow-up for the hip ranged from 77 to 98 (average, 92); 31 cases were rated as excellent, 6 as good, 2 as fair and one as poor, giving an excellent to good rate of 92.5%. Conclusion:In the treatment of femoral neck fracture of Garden type Ⅳ which is difficultly reducible in young and middle-aged patients, if closed reduction has failed, open reduction and cannulated screw fixation directly via the anterior approach can achieve satisfactory short-term outcomes because it facilitates fracture reduction and fixation under direct vision, promotes fracture union and reduces avascular necrosis of the femoral head.

OBJECTIVETo explore the protective effects of extract of Ginkgo biloba (EGB) in adriamycin (ADR)-induced heart failure (HF) and the mechanism of ghrelin peptide.

METHODWistar rats were randomly divided into three groups: control group, HF group and EGB group. ADR was injected in the rats of HF group and EGB group by caudal vein. After the last injection, the rats in EGB group were given intra-gastric administration of EGB solution (100 mg x kg(-1) x d(-1)). Three weeks later, cardiac function was detected; Ghrelin levels in plasma and myocardium were measured by radio-immunology assay (RIA); High energy phosphates (HEP) contents in myocardium were measured by HPLC; Myocardial gene expression of ghrelin was measured by RT-PCR.

RESULTCompared with control group, HF group had obviously decreased index of cardiac function, and these indexes such as +/- dp/dt max in EGB group were higher than those in ADR group. Plasma ghrelin level in HF group was higher than that in control group while myocardial ghrelin level was significantly lower than that in control group. Myocardial ATP content and gene expression of ghrelin mRNA in HF group were significantly lower than those in control group; Plasma ghrelin level in EGB group was significantly increased. Myocardial ATP content and gene expression of ghrelin mRNA in EGB group were significantly higher than those in HF group, and were closed to those of control group.

CONCLUSIONMyocardial energy dysfunction is an important reason of ADR-induced HF. EGB therapy can improve cardiac function and energy metabolism in HF rats, partly because it might increase the expression and production of ghrelin, which can promote positive energy metabolism.

Animals ; Disease Models, Animal ; Doxorubicin ; adverse effects ; Gene Expression ; drug effects ; Ghrelin ; metabolism ; Ginkgo biloba ; chemistry ; Heart Failure ; drug therapy ; genetics ; metabolism ; Humans ; Male ; Myocardium ; metabolism ; Plant Extracts ; administration & dosage ; Protective Agents ; administration & dosage ; Random Allocation ; Rats ; Rats, Wistar