the GGT level.Increased GGT and TG may be risk factors for diabetes mellitus.

Objective To observe theRuangan granule on liver fibrosis in rats liver pathology change, the influence of hepatic function and hepatic fibrosis indexes, and to discusses the mechanism of its action to provide the basis for clinical prevention and treatment of liver fibrosis.Methods A total of 105 Wistar rats were randomly divided into a normal control group, a model group and a colchicines group, and Dahuang-Zhechong pill group, high-, medium- and low-doseRuangan granule groups (n=15 in each group). Liver fibrosis was induced by carbon tetrachloride and a high-cholesterol diet. After modeling, the low-, medium- and high-doseRuangan granule groups were intragastric administratedRuangan granule mixed suspension 3.6, 7.2, 14.4 g/(kg?d), respectively;Dahuang-Zhechong pill group was administrated with Dahuang-Zhechong pellets mixed suspension of 0.18 g/(kg?d); the colchicine group was intragastric administrated with colchicine mixed suspension of 0.108 mg/(kg?d); and the normal control group and the model group were intragastric administrated with the equal volume of distilled water. All rats were intragastric administrated for 8 weeks. HE staining and Masson trichromatic collagen staining were used to observe the pathological changes of liver While the change of AST, ALT, PH, TP and serum HA, LN, C-Ⅳ, PCⅢin blood serum were detected. Results Masson trichromatic collagen staining showed that, the percentage of liver collagen fiber area in rats of theRuangan granule high-dose group was significantly decreased (7.06 ± 1.18) % compared with model group (23.49 ± 1.34) %, colchicine group (11.35 ± 1.83) %, rhubarb worm pill group (15.27 ± 1.22) %,Ruangan granule medium-dose group (14.52 ± 1.75) %, and low dose group (16.08 ± 1.56) % (P<0.05 orP<0.01). Compared with model group,Ruangan granule high-dose group rats serum AST (75.86 ± 5.23 U/Lvs. 157.62 ± 24.04) U/L, the ALT (80.15 ± 5.94 U/Lvs. 160.58 ± 26.47) U/L, PH (52.58 ± 4.98μg/Lvs. 98.66 ± 6.75)μg/L significantly reduced, TP (74.19 ± 3.56 g/Lvs. 51.73 ± 5.92)g/L increased significantly (P<0.01).Ruangan granule high-dose group rats serum HA (277.22 ± 106.34 ng/mlvs. 553.19 ± 172.38 ng/ml), LN (89.82 ± 5.68 ng/mlvs. 134.25 ± 10.64 ng/ml), C-Ⅳ (47.94 ± 8.65 ng/mlvs. 84.18 ± 13.83 ng/ml), PCⅢ (16.53 ± 4.88 ng/mlvs.31.57 ± 5.35 ng/ml) decreased significantly in the model group (P<0.01).ConclusionRuangan granule has obvious effects for resisting liver fibrosis.

Objective To investigate the effects of Ruangan granule on transforming growth factor-β1(TGF-β1)/Smads signaling pathway in liver fibrosis in rats. Methods A total of 105 Wistar rats were randomly divided into normal control group, model group and colchicine, Dahuang-Zhechong pill group, high-, medium- and low-dose Ruangan granule groups (n=15 in each group). Liver fibrosis was induced by carbon tetrachloride and a high-cholesterol diet. After modeling, the low-, medium- and high-dose Ruangan granule groups were intragastric administrated Ruangan granule mixed suspension 3.6, 7.2, 14.4 g/(kg?d), respectively;Dahuang-Zhechong pill group was administrated with Dahuang-Zhechong pellets mixed suspension of 0.18 g/(kg?d);the colchicine group was intragastric administrated with colchicine mixed suspension of 0.108 mg/(kg?d);and the normal control group and the model group were intragastric administrated with the equal volume of distilled water. All rats were intragastric administrated for 8 weeks. The expressions of TGF-β1, Smad3 and Smad7 proteins in the liver tissue were detected with immunohistochemical staining method. The expressions of TGF-β1, Smad3, Smad7 mRNAs in the liver tussue were detected by RT-PCR. Results The expressions of TGF-β1 (2.59 ± 0.99 vs. 0.43 ± 0.21) and Smad3 (2.56 ± 0.67 vs. 0.41 ± 0.18) proteins and TGF-β1 mRNA (2.25 ± 0.21 vs. 0.71 ± 0.09) and Smad3 (2.34 ± 0.03 vs. 0.78 ± 0.12) mRNAs in the model group were significantly increased than those in the normal control group (all P<0.01). Compared with the model group, the expressions of TGF-β1 (1.12 ± 0.27 vs. 2.59 ± 0.99) and Smad3 (1.05 ± 0.34 vs. 2.56 ± 0.67) proteins in the high-dose Ruangan granule group decreased significantly, the expression of Smad7 increased significantly (2.33 ± 0.62 vs. 0.36 ± 0.18), and the expressions of TGF-β1 (1.09 ± 0.11 vs. 2.25 ± 0.21) and Smad3 (1.10 ± 0.02 vs. 2.34 ± 0.03) mRNAs decreased significantly, the expression of smad7 mRNA (1.18 ± 0.13 vs. 0.38 ± 0.11) increased significantly (P<0.05). Conclusions Ruangan granule can regulate the TGF-β1/Smads signaling pathway via down-regulation of TGF-β1, Smad3 and up-regulation of Smad7 in liver fibrosis in rats.

This study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. One thousand and six hundred drugs were screened using the ZEBOV-GP/HIV model, a pseudovirus formed by an HIV-core packed with the Zaire Ebola virus glycoprotein. We identified 12 gonadal hormone drugs with inhibitory activities in ZEBOV-GP/HIV entry at final concentration of 10 μmol x L(-1). Among them, three drugs exhibited strong activities with IC50 < 1 μmol x L(-1), such as toremifene citrate (IC50: 0.19 ± 0.02 μmol x L(-1)), tamoxifen citrate (IC50: 0.32 ± 0.01 μmol x L(-1)) and clomiphene citrate (IC50: 0.53 ± 0.02 μmol x L(-1)); seven drugs had moderate activities with IC50 between 1 and 10 μmol x L(-1), such as estradiol benzoate (IC50: 1.83 ± 5.69 μmol x L(-1)), raloxifene hydrochloride (IC50: 3.48 ± 0.07 μmol x L(-1)), equilin (IC50: 4.00 ± 9.94 μmol x L(-1)), estradiol (IC50: 5.26 ± 9.92 μmol x L(-1)), quinestrol (IC50: 6.36?5.37 gmol-L1), estrone (IC50: 6.87 ± 0.03 μmol-L1) and finasteride (IC50: 9.94 ± 0.45 μmol x L(-1)); two drugs, hexestrol (IC50: 14.20 ± 0.55 μmol x L(-1)) and chlormadinone acetate (IC50: 24.60 ± 0.36 μmol x L(-1)), had weak activities against ZEBOV. Further, toremifene citrate, tamoxifen citrate, clomiphene citrate, raloxifene hydrochloride and quinestrol could block both pseudovirus type Sudan ebola virus (SEBOV-GP/HIV) and Marburg virus (MARV-GP/HIV) entries.
Antiviral Agents ; pharmacology ; Drug Evaluation, Preclinical ; Ebolavirus ; drug effects ; physiology ; Hemorrhagic Fever, Ebola ; Humans ; Marburgvirus ; drug effects ; physiology ; Selective Estrogen Receptor Modulators ; pharmacology ; Virus Internalization ; drug effects

Objective To investigate the effect of early systemic nursing intervention applied by ward nurse on constipation among patients with depression. Methods A total of 144 participants were divided into the intervention group (72 cases) andthe control group (72 cases) by random number table. Except for a period of 4 weeks routine nursing and 4 weeks follow-up observation which were applied for control subjects, systemic nursing interventions werealso conducted inintervention patients. The incidence of constipation and constipation symptom scoreswere measured at the ends of the 4th and 8th week of treatment. Results The incidences of constipation and constipation symptom scores of the 4th and 8th weekend in the intervention group were 17.6% (12/68), 6.59 ± 4.08, 23.5% (16/68) and 6.81 ± 3.99 respectively. While in the control group they were 34.9%(22/63), 8.84 ± 4.45, 44.4%(28/63) and 10.52 ± 3.86 respectively. These differences between two groups at the 4th and 8th weekend were all significant (χ2=5.077, t=3.023, P < 0.05 and χ2=6.413, t=5.411, P < 0.05, respectively). Compared with the 4th weekend, in the 8th weekend, constipation rate and scores of constipation symptom were increased in thecontrol group (P < 0.05), but not in theintervention group (t=-1.965, P > 0.05). Conclusions In patients with depression, early systemic nursing intervention can effectively ameliorate the constipation caused by amitriptyline.

ObjectiveTo seek experimental evidence of epidermal barrier dysfunction in psoriasis,and to provide a basis for adjuvant therapy of psoriasis.MethodsPhysiometric methods were used to determine the value of sebum content,transepidermal water loss(TEWL) and water content of stratum corneum in 60 patients with psoriasis and 48 normal human controls.The ultrastructure of lamellar bodies was observed with transmission electron microscopy,and the expression of acid ceramidase in normal skin and psoriatic lesions was detected by using immunohistochemical techniques.ResultsCompared with the normal skin,TEWL value was increased(P ＜ 0.01),but water content of stratum corneum decreased(P ＜ 0.01 ) in psoriatic lesions,and sebum content was similar between normal skin and psoriatic lesions.As electron microscopy showed,lamellar bodies in keratinocytes were reduced in number with a disorganized arrangement and irregular size in psoriatic lesions.The expression of acid ceramidase also decreased in psoriatic epidermis.Conclusions The function of epidermal barrier in psoriasis is impaired,and to restore epidermal barrier function and enhance hydration may serve as an important adjuvant therapy of psoriasis.

Objective To evaluate the effects of Prinsepia utilis Royle oil (PURO) on the synthesis of ceramide and expression of acid ceramidase N-acylsphingosine amidohydrolase 1 (ASH1),and to explore the mechanisms underlying its moisturizing and skin barrier-repairing effects.Methods Keratinocytes from human foreskin tissue were classified into 2 groups to be cultured in keratinocyte-serum free medium (K-SFM) with or without the presence of PURO.Enzyme linked immunosorbent assay (ELISA) was performed to measure the level of ceramide in the culture supernatant of keratinocytes at 0,3,8,24 and 48 hours.The back of nude mice was divided into 4 areas,i.e.,test area,matrix area,blank control area and negative control area.Acetone and ether were used to destroy the epidermal barrier in the test,matrix,and blank control areas,then,the former 2 areas were topically treated with emulsions containing 1％ PURO and matrix,respectively,and the blank control area remained untreated.The epidermal barrier remained intact and untreated in the negative control area.Noninvasive methods were used to determine transepidermal water loss (TEWL),epidermal moisture content and skin lipid content in these areas on day 0,1,3,and 7.Skin tissue was obtained from these areas on day 0 and 7 followed by an immunohistochemical study for the quantification of ASH1 expression.Results The level of supernatant ceramide increased with time in the PURO-treated keratinocytes,which was significantly higher at 24 hours and 48 hours than at 0 hour (1.3817 ± 0.100 and 1.3737 ± 0.047 vs.0.7630 ± 0.143,both P ＜ 0.05).The supernatant ceramide was also elevated in the PURO-treated keratinocytes compared with untreated keratinocytes at 24 and 48 hours (both P ＜ 0.05).Noninvasive skin tests showed a gradual decrease in the TEWL,but an increase in the epidermal moisture content and skin lipid content with time in the 3 epidermal barrier-destroyed areas.As far as the test area was concerned,TEWL value was significantly lower on day 3 and 7 than on day 0 (10.85 ± 0.64 and 8.01 ± 0.58 vs.12.65 ± 0.71,both P ＜ 0.05),while a significant increment was observed in the skin lipid content on day 3 and 7 compared with day 0 (29.14 ± 0.40 and 31.30 ± 0.88 vs.27.02 ± 0.65,both P ＜ 0.05),as well as in the epidermal moisture content on day 1,3 and 7 compared with day 0 (13.98 ± 0.28,15.00 ± 0.38 and 15.86 ± 0.18 vs.11.74 ± 0.62,all P＜ 0.05).On day 7,there was a statistical decline in TEWL value,but an elevation in epidermal moisture content,skin lipid content and ASH1 expression in the test area compared with the matrix area and blank control area (all P ＜ 0.05).Also,the expression of ASH1 was upregulated on day 7 compared with day 0 in the 3 barrier-destroyed areas (all P ＜ 0.05).Conclusion PURO may exert skin-moisturizing and barrier-repairing effects by enhancing the synthesis of ceramide and expression of acid ceramidase ASH1.

Objective To investigate the correlation of epidermal distribution of lamellar bodies and expression of ceramidase with skin barrier dysfunction in polymorphous light eruption.Methods Forty-seven patients with polymorphous light eruption and 40 healthy volunteers were recruited into this study.Noninvasive instruments were used to measure skin sebum content,transepidermal water loss(TEWL)and water content in stratum corneum in all of the subjects.Then,tissue specimens were obtained from the lesions at sunexposed sites in the patients and normal skin of the healthy volunteers.The ultrastructure and distribution of lamellar bodies were observed with transmission electron microscopy in five lesion and control specimens.Immunohistochemistry was performed to detect the expression of ceramidase in the tissue specimens.Results Compared with the normal skin from healthy volunteers,the lesions from patients showed decreased number of lamellar bodies in the granular layer and prick cell layer with a disorganized arrangement.Ceramidase was positively expressed in 20 lesion specimens and 36 normal control specimens,weakly expressed in 21 lesion specimens and 4 normal control specimens,and negative in 6 lesion specimens; there was a significant difference in the expression of ceramidase between the lesion specimens and normal control specimens(P ＜ 0.01).The lesions also showed high TEWL(34.2191 ± 12.70 vs.16.8350 ± 6.50,P ＜ 0.01),lower water content in stratum corneum(22.7319 ± 8.71 vs.29.4250 ± 5.08,P ＜ 0.01)and similar skin sebum content compared with the normal skin.Conclusions There is a disturbance in the synthesis of ceramide in patients with polymorphous light eruption,which may contribute to the impairment of skin barrier.

Bibliometrics ; Financial Management ; Medicine, Chinese Traditional ; Periodicals as Topic ; Research Support as Topic

Background The main cause of filtering surgery failure is over proliferation of fibroblasts in filtering channels,leading to excessive fibrosis and scar formation.Researches determined that p38 mitogen-activated protein kinase(MAPK) signaling pathway plays an important role in fibroblast phenotype transition. Objective The present study was to investigate the inhibitory effect of p38 MAPK inhibitor on myofibroblasts transdifferentiation and the extracellular matrix synthesis after filtration surgery in rabbit eyes. Methods Trabeculectomy was performed on 24 eyes of 12 clean New Zealand white rabbits to establish the filtering operative models.The models were randomized into model group,SB203580 group and mitomycin C ( MMC ) group.1 ml SB203580 ( 0.2 g/L) was conjunctively injected at the end of operation in the rabbits of the SB203580 group,and the cotton piece with 0.2 g/L MMC solution was placed on the operative area for 3 minutes intraoperatively in the rabbits of the MMC group.The bleb appearances were examined under the slit lamp microscope,and intraocular pressure(IOP) was measured with Icare tonometer I,3,7,10,14 days after operation.0.2 ml aqueous humor was extracted and the conjunctive tissue at the filtering area was obtained 14 days after operation for the detection of α-smooth muscle actin (α-SMA) and fibronectin protein by ELISA.Expression of ACTA2 mRNA,connective tissue growth factor(CTGF) mRNA and alpha2 chain of type Ⅰ collagen( COL1A2 )mRNA in conjunctive tissue was assayed with fluorescence real-time PCR. Results Vascularization of fibrosis of filtering bleb were obvious in the eyes of the model group,and the bleb was flat and diffuse in the eyes of the SB203580 group and MMC group on 14 days following operation.No significant difference was seen in IOP before trabeculectomy among these three groups( F=0.065,P=0.937 ).IOP was gradually elevated with the increase of time after operation ( F =32.873,P =0.030 ).ELISA assay showed that α-SMA level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group( P＜0.05 ).Fibronectin level in conjunctiva was lower in the SB203580 group and MMC group compared with the model group,and that of MMC group was significant lower than the SB203580 group (P＜0.05).Fluorescence real-time PCR showed that expressions of the ACTA2 mRNA,CTGF mRNA and COL1A2 mRNA were significantly different among the three groups( P＜0.01 ),with the highest expression in model group and the lowest expression in the MMC group ( P ＜ 0.05 ). Conclusions Fibrotic reaction after trabeculectomy can be suppressed by inhibiting p38 MAPK signal pathway.The mechanism of SB203580 is to reduce the synthesis of myofibroblasts transdiffercntiation and extracellular matrix.