To investigate the therapeutic effect and molecular mechanism of the main flavonoid components of Silybum marianum (S. marianum) on nonalcoholic fatty liver disease (NAFLD), we identified nine flavonoids in S. marianum through TCMSP, PubChem database and corresponding literatures. The potential therapeutic targets of NAFLD were predicted by SwissTargetPrediction, GeneCards and Venny 2.1.0 platform, while the protein-protein interaction (PPI) network of potential targets was analyzed using String platform and Cytoscape software. Then GO and KEGG pathway enrichment analysis were performed using David 6.8 database, followed by molecular docking verification using AutoDock software. In vitro, components with higher degree value in the "components-targets-pathway" network were chosen for further analysis. L02 cells were used to establish lipid accumulation model and treated with different components. Furthermore, the effects of four pure active compounds from S. marianum on lipid accumulation in hepatocytes were analyzed by oil red O staining. The results showed that the main nine flavonoids extracted from S. marianum contained 24 potential NAFLD targets. Several critical pathways closely related to NAFLD process were identified by GO and KEGG enrichment analysis, including phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) pathway, type 2 diabetes pathway, tumor necrosis factor (TNF) pathway and insulin resistance pathway. The results of molecular docking further indicated that the core components displayed strong binding abilities with key targets respectively, and silandrin showed better binding activity as compared to other components. The results obtained from L02 cells showed that the lipid accumulation was reduced by treatment with isosilybin A, isosilybin B, silydianin and silychristin, while the activity of isosilybin B was better than that of isosilybin A. Taken together, we concluded that the main flavone components of S. marianum could improve lipid accumulation through multiple signaling pathway in hepatocytes, and this could be a potential new strategy for the treatment of NAFLD.

Aim To observe the protective effects of probiotics on alcoholic liver injury in rats .Methods Male Wistar rats were randomly divided into the follow-ing three groups: control group , normal diet with nor-mal (5 ×108 CFU· kg -1· d -1) treatment group.Ex-cluding the rats in the normal control group , the other animals were initially received intragastric administra-tion with 56%( V/V) ethanol 5.5~11.0 mL· kg -1 · day -1 for 8 weeks.Then the rats’ faeces were collect-ed, and the liver and the small intestine were obtained for pathologic and ultrastructural observation .Serum ALT, AST and ALP was measured by method of bio-chemistry .Serum DAO and D-LA was measured by en-zyme linked immunosorbent assay .The expression of FOXO4 in small intestine was detected by immunohis-tochemistry .The intestinal flora genome DNA was ex-tracted from faeces and the sequence of 16 S rDNA was analyzed by high-throughput sequencing technologies . Results Hepatic steatosis was obviously improved in probiotics treatment groups compared with ethanol-trea-ted group , and the ultrastructural such as mitochondri-al and rough endoplasmic reticulum pathological chan-ges was significantly alleviated . The ultrastructural changes in intestinal were better in probiotics treatment group than in the ethanol-treated group .And ethanol-induced rats ’ serum ALT, AST, ALP, D-LA and DAO levels showed a significant reduction in the probi-otics treatment groups compared with the ethanol-trea-ted group ( P<0.05 ) .The FOXO4 expression was in-creased obviously in the probiotics treatment groups compared with the ethanol-treated group ( P <0.05 ) . And the intestinal flora diversity was impacted after feeding alcohol , and probiotics had a certain regulative action in helping the intestinal flora back to normal state; At phylum level , the Firmicutes quantity was lower and the Bacteroidetes quantity was higher in eth-anol-treated group than those in the control group ( P<0.05 ) , and the conditions were improved after supple-menting probiotics .At genus level , the percent of ge-nus abundance was similar to normal control group in the probiotics treatment groups compared with the etha-nol-treated group .Conclusion Probiotics can relieve liver injury induced by alcohol in rats , and the mecha-nism may be related to the modulation of probiotics on the intestinal flora distribution and intestinal barrier .

This study is to determine age-specific prostate-specific antigen (PSA) distributions in Chinese men without prostate cancer (PC) and to recommend reference ranges for this population after comparison with other studies. From September 2003 to December 2006, 9 374 adult men aged from 18 to 96 years agreed to participate in the study. After all cases of PC were excluded, 8 422 adult men participated in statistical analysis and were divided into five age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each age group. The age-specific PSA reference ranges are as follows: 40-49 years, 2.15 ng mL(-1); 50-59 years, 3.20 ng mL(-1); 60-69 years, 4.10 ng mL(-1); 70-79 years, 5.37 ng mL(-1). The results indicate that the ethnic differences in PSA levels are obvious. The currently adopted Oesterling's age-specific PSA reference ranges are not appropriate for Chinese men. The reference ranges of this study should be more suitable to Chinese men.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging ; blood ; ethnology ; China ; Humans ; Male ; Middle Aged ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; blood ; diagnosis ; ethnology ; Reference Values ; Retrospective Studies ; Young Adult

Based on variation of Pinus massoniana families, heritablility and correlation analysis, the contents of shikimic acid and procyanidine (heritability 0.90, 0.70), dry weight of single branch (heritability 0.60) and and leaf length (heritability 0.46) were screened out as quality, yield and harvest cost traits of Folium Pini, respectively. For the different medicinal application of Folium Pini, varied methods were chosen to estimate weight and construct index equation. Weight adjustment based.on equal emphasis were used as economic weight determining method to select the best families, and the index (accuracy 0. 936 4 and heritability 0. 881 6) obtained was a little better than that obtained by equal emphasis, and much better than that by restricted index. The superior families selected with adjustment weight and equal emphasis were No. 46, 43 and 28. Partial regression were used as economic weight determining method to select the best families,and the index obtained had the highest accuracy (0.941 5) , index heritability (0. 889 9) and the genetic gain of shikimic acid content. The superior families selected with this method were No. 46, 27 and 47. No. 46 was the best families with maximal economic benefit. Our study indicated that suitable method for estimate weight and construct index equation can be applied for better accuracy of superior families selection of P. massoniana.
Breeding ; Drugs, Chinese Herbal ; analysis ; Pinus ; chemistry ; classification ; genetics ; growth & development ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; classification ; genetics ; growth & development

OBJECTIVETo explore the characteristics of distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR) and mismatch negativity (MMN) in guinea pigs with hyperbilirubinemia and assess the impact of hyperbilirubinemia on their hearing functions.

METHODNormal neonatal guinea pigs were randomly divided into normal control, low- and high-dose bilirubin groups. DPOAE, ABR and MMN were tested and compared between the 3 groups of guinea pigs.

RESULTSThe DPOAE was comparable between the 3 groups (P>0.05). The guinea pigs with peritoneal injection of low-dose bilirubin exhibited significantly prolonged wave III and V latencies and I-III interwave intervals during the ABR test in comparison with the control group (P<0.05). All the ABR parameters were significantly different between the high-dose bilirubin group and the control group (P<0.05). The detection rates of MMN were significantly different between the 3 groups (Chi(2)=7.438, P=0.024), and the average MMN latency was significantly shorter in the control group than in the high-dose group (P<0.05), but the amplitudes of MMN remained similar between the 3 groups (P>0.05).

CONCLUSIONSHyperbilirubinemia results impairment primarily of retrocochlear auditory pathway with relative mild damage of the cochlear. Apart from sensorineural auditory impairment, hyperbilirubinemia may also cause central auditory processing abnormalities.

Animals ; Behavior, Animal ; Bilirubin ; blood ; Evoked Potentials, Auditory, Brain Stem ; Female ; Guinea Pigs ; Hyperbilirubinemia ; blood ; physiopathology ; Male ; Otoacoustic Emissions, Spontaneous

Objective To compare antitussive and expectorant effects between endophytes from Glycyrrhiza uralensis and decoction,and filtrate effective strains.Methods A total of 84 Kunming mice were randomly divided into blank group,positive control group,Glycyrrhiza decoction group,3 groups of endophytes (JTYB006 group,JTYB029 group,JTYF023 group).There are two batches of mice altogether.Blank group was given the injection of 0.9％ NaCl.Positive control group was given 30 mg · kg-1 codeine phosphate tablets.Glycyrrhiza decoction group was given 1.3 g · kg-1 wild Glycyrrhiza decoction.Three groups of endophytes were respectively given 1.3 g · kg-1 powder of endophytes.Six groups were given the corresponding dose by intragastric administration once a day,for 7 days.1 hour after the last medication,the mice cough models were respectively induced by ammonia and SO2.The antitussive effects were evaluated by median effective dose time (EDT50),R-value,the incubation period of cough,the times of cough within 2 minutes,inhibition ratio of cough and extension ratio of cough.70 Wistar rats were randomly divided into 7 groups,these were blank group,model group,positive control group,Glycyrrhiza decoction group,3 groups of endophytes(JTYB006,JTYB029,JTYF023).The rat model of phlegm blocking in lung was established by inhaleing SO2 and clod wind for 10 days.10 days later,the blank group was given the injection of 0.9％ NaCl,positive control group was given 0.08 mg · kg-1 compound bulbus fritilillariae cirr hosate and ammonium chloride tablets,Glycyrrhiza decoction group was given 0.95 g · kg-1 wild Glycyrrhiza decoction,3 groups of endophytes were respectively given 0.95 g · kg-1 powder of endophytes.Seven groups were given the corresponding dose by intragastric administration once a day for 7 days.The general activities,the amount of phlegm and pathological of lung tissues were measured.In addition,the levels of nitric oxide (NO),tumor necrosis factor (TNF-α),interleukin-17 (IL-17) and IL-23 were measured by enzyme-linked immunosorbent (ELISA) method.Results The EDT50 in blank group was 13.00 s,which in positive control,Glycyrrhiza decoction,JTYB006,JTYB029,JTYF023 groups were 30.09,20.32,18.45,25.03,16.52 s,the EDT50 of all drug intervention groups extended.Positive control,Glycyrrhiza decoction and JTYB029 groups had the obvious effect (R ＞ 150),JTYB006 had the effect of relieving cough (130 ＜ R ＜ 150),JTYF023 was invalidity(R ＜ 130).For cough caused by SO2,the incubation period of cough in blank group was (14.67 ± 7.20) s and positive control,Glycyrrhiza decoction,JTYB006,JTYB029 groups (28.00 ± 8.15),(25.83 ±9.35),(20.58 ±6.52),(26.50 ±5.32)s with statistically significant difference (P ＜0.01 or P ＜0.05).The times of cough within 2 minutes in blank group was(78.92 ± 19.06) and positive control,Glycyrrhiza decoction,JTYB006,JTYB029 groups were (47.42 ± 19.96),(57.67 ± 19.04),(63.15 ± 15.30),(44.25 ± 16.87) with statistically significant difference (P ＜ 0.01 or P ＜ 0.05).Compared with Glycyrrhiza decoction,JTYB006 and JTYF023 had remarkable short on the incubation period of cough,JTYB029 had remarkable reduction on the times of cough within 2 minutes(P ＜0.01 or P ＜0.05).In model,positive control,Glycyrrhiza decoction and JTYB029 groups,the amount of phlegm were (14.47 ± 3.30),(7.26 ± 4.55),(8.45 ± 3.78),(8.23 ± 1.19) mm,the levels of NO were (51.57±8.33),(30.02 ±2.65),(39.10 ±9.63),(39.25 ± 10.20)μmol · L-1,the levels of TNF-α were (654.80±56.40),(282.56 ±70.81),(400.24 ±78.03),(410.86 ±68.74) ng· mL-1,the levels of IL-17 were (66.28 ±9.34),(39.10 ±6.27),(50.20 ±9.05),(48.70 ± 10.28)pg · mL-1,the levels of IL-23 were (29.04 ±3.55),(16.02 ±3.60),(20.11 ±2.96),(21.25 ±3.40)pg · mL-1 Compared with the model group,Glycyrrhiza decoction and JTYB029 had remarkable decreasions in the terms of the amount of phlegm and the levels of NO,TNF-o,IL-17 and IL-23 (P ＜ 0.01 or P ＜ 0.05).Conclusion By filtrating,2 endophytes from Glycyrrhiza uralensis (JTYB006,JTYB029) have antitussive effects,and 1 endophytes from Glycyrrhiza uralensis (JTYB029) has expectorant effects.The antitussive and expectorant effects have no significant difference between wild Glycyrrhiza'decoction and JTYB029.

OBJECTIVETo investigate the clinicopathologic characteristics of primary nasopharyngeal adenoid cystic carcinoma (NPACC) and its relation to Epstein-Barr virus (EBV) infection in Guangzhou where is a high-incidence area of EBV-associated nasopharyngeal carcinoma (NPC).

METHODS17 cases of NPACC with clinical record and biopsy samples were collected in Guangzhou and their clinical manifestations were reviewed. Besides HE, Alcian blue and PAS, LSAB immunohistochemistry was performed for detecting the expression of a variety of epithelial markers, CD21 and EBV encoded LMP1. EBV encoded early RNAs (EBER) was detected by using in-situ hybridization. Nested PCR was applied for studying the presence of EBV W-fragment in tissues.

RESULTSThe ratio of male to female was 7:10. The patients' age ranged from 30 to 63 years, and the median age was 46 years. 14 out of 17 tumors showed markedly local aggressive growth, presenting as T3 or T4. However, only 1 patient had metastasis of an ipsilateral cervical lymph node. The majority of neoplastic cells were basal-cell like in shape and with scanty cytoplasm and a deeply stained nucleus. Intercellular hyaline or mucinous substance was always present in between the carcinoma cells. Cribriform structure formed by the neoplastic cells could be found in 16 out of these 17 biopsies. The NPACC always express the wide-spectrum cytokeratin and the epithelium membrane antigen. Only a few or a small number of carcinoma cells showed nuclear EBER-signals in 9 cases (9/17). Concurrently, these 9 NPACCs showed a 192 bp W-fragment positive band on electrophoresis gel by nested PCR. LMP1 expression had been found in 5 out of the 9 NPACCs (55.6%) accompanying with EBER-positive carcinoma cells. The EBER-positive infiltrating lymphocytes could also be found in the stroma of 3 out of the 9 EBER-stained NPACC slides. All the tumor cells, including the EBER-positive cell of the 17 NPACCs showed no CD21 expression.

CONCLUSIONSThe female is predominant over the male in development of NPACC, which often accompanied with a markedly invasive capacity at the nasopharynx and its neighboring sites. Only a small number of tumor cells, nearly a half of the studied cases were infected with EBV. Therefore, it's postulated that there seems no close relation present between NPACC and EBV infection.

Adult ; Carcinoma, Adenoid Cystic ; etiology ; pathology ; Epstein-Barr Virus Infections ; complications ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; etiology ; pathology ; RNA, Viral ; analysis ; Viral Matrix Proteins ; analysis

OBJECTIVETo explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK).

METHODSSeventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction.

RESULTS1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued.

CONCLUSIONSReasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

Administration, Oral ; Adult ; Azathioprine ; administration & dosage ; Cyclosporine ; administration & dosage ; Diabetic Nephropathies ; surgery ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; administration & dosage ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; Prednisolone ; administration & dosage ; Retrospective Studies ; Transplantation, Homologous

OBJECTIVETo analyze the global gene expression profile of primary cultured nasopharyngeal carcinoma (NPC) cells using cDNA microarray techniques to screen new candidate genes related to the occurrence and progression of NPC.

METHODSA NPC cell line C666 and primary cultured NPC cells from biopsy specimens in 5 cases were analyzed with microarray techniques in comparison with 3 normal nasopharyngeal epithelial (NPE) biopsy specimens. Several differentially expressed genes identified from the microarray results were verified by fluorescence real-time PCR (FQ-PCR) and immunohistochemistry (IHC).

RESULTSPrimary cultured cells of both NPC and NPE were verified by cytokeratin IHC, EBER1 in situ hybridization and EBV-DNA real-time PCR. Compared with NPE cells, a total of 493 genes in at least 4/6 of the samples were identified to be differentially expressed in the primary cultured NPC cells, including 264 up-regulated and 229 down-regulated ones. Several differentially expressed genes according to the microarray results were confirmed by real-time PCR and IHC.

CONCLUSIONcDNA microarray technique provides an effective and accurate means for global gene expression profiling of primary cultured NPC cells to screen the differentially expressed genes, which may serve as an important basis for studying the mechanism, classification and diagnosis of NPC at the molecular level.

Animals ; Cells, Cultured ; Gene Expression Profiling ; Humans ; Immunohistochemistry ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; RNA ; isolation & purification

The process of injury and repair in airway epithelium involves cell spreading and migration followed by cell proliferation. IQ domain GTPase-activating protein 1 (IQGAP1) acts in a series of cell processes, but has not been clarified in lung epithelial cells. In this study, a widely used model of injury and repair in vitro by scratching bronchial epithelial cells (BECs) was utilized to investigate the function of IQGAP1. The results showed that IQGAP1 was abundant in BECs of mouse, rat, pig and human. IQGAP1 was colocalized with tubulin cytoskeleton, but was destroyed by nocodazole, a microtubule disassembly reagent. IQGAP1 mRNA and protein expressions increased at 6-9 h after scratching. In addition, overexpression of IQGAP1 translocated β-catenin from the cytoplasm into the nucleus and activated the Tcf/Lef signal. Scratching altered the associations of IQGAP1 with β-catenin, adenomatous polyposis coli (APC) and cytoplasmic linker protein-170 (CLIP-170). Silencing IQGAP1 expression by small interference RNA (siRNA) blocked the wound closure. It is concluded that IQGAP1 signal is involved in the wound closure of BECs induced by scratching.
Adenomatous Polyposis Coli Protein ; metabolism ; Animals ; Bronchi ; cytology ; Cell Proliferation ; Cells, Cultured ; Cytoskeleton ; metabolism ; Epithelial Cells ; cytology ; pathology ; Humans ; Mice ; Microtubule-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Nocodazole ; pharmacology ; Rats ; Swine ; Tubulin ; metabolism ; beta Catenin ; metabolism ; ras GTPase-Activating Proteins ; metabolism