Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect.Nevertheless,the mechanism is not completely identified.This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats.The liver fibrosis model was made by the subcutaneous injection of CCl4.The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer.Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry.Expression levels of TGF-β1,Smad2/3,phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis.Results showed that melatonin suppressed CC14-induced liver fibrosis,along with an improvement in histological changes,significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver.Melatonin improved liver function indicated by decreased serum ALT and AST activities.In addition,melatonin exerted its anti-oxidant effects,as supported by decreased MDA levels and increased GPx activities in liver.Furthermore,melatonin inhibited TGF-β1/Smad pathway,as evidenced by decreased TGF-β1,Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver.In conclusion,melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway.It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

We isolated 61 endophyte isolates from the bark of 4 plants, Ginkgo biloba L, Albizzia julibrissin Durazz, Ailanthus sltissima (Mill) Swingle and Melia azedarach L. At the test concentration of 200 ?g/mL, higher than 50% of antitumor activities were demonstrated with crude extracts from 45.9% of fungal culture in MTT assay. Six isolates, YX5, YX17, YX36, KL1, CC1 and CC5, still showed higher cytotoxicity at 50 ?g/mL. No isolates from A. julibrissin had inhibitory effect towards EC109 at the test concentration of 50 ?g/mL; while about 15.8% of isolates from G. biloba were active. IC50 of the extract from the most active isolate YX5 against EC109, HONE1 and HeLa were 18.3 ?g/mL, 3.6 ?g/mL and 6.5 ?g/mL, respectively. Our results indicate that endophytes from G. biloba could be regarded as a potent source of antitumor drugs.

In this study, researchers adopted the network analysis method to study Buyang Huanwu decoction at three levels, namely chemical ingredients, targets and diseases, and discovered the potential effect of Buyang Huanwu decoction in cancer treatment. Besides, they analyzed the "target-target" network of Buyang Huanwu decoction based on diseases, calculated four network indexes, namely node centrality, closeness centrality, betweenness centrality and eigenvector centrality for a comprehensive evaluation on the importance and significance of each target in the network. Afterwards, key targets of Buyang Huanwu decoction were excavated to obtain two important targets--COX-2 and PPAR-gamma, which may be important targets involved in the qi deficiency and blood stasis diseases. Meanwhile, the two targets were the basis to build the core network of "chemical component-target-disease" of Buyang Huanwu decoction, which provided reference for further studies on the effect of Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases. According to the study, the network analysis method was helpful to excavate potential targets Buyang Huanwu decoction in treating qi deficiency and blood stasis diseases, and could provide methodological reference for revealing the mechanism of Buyang Huanwu decoction at multiple levels, with a guiding significance for interpreting mechanisms of traditional Chinese medicinal formulae and developing new drugs.
Drugs, Chinese Herbal ; pharmacology ; Hematologic Diseases ; drug therapy ; Medicine, Chinese Traditional ; Qi ; Yang Deficiency ; drug therapy ; Yin Deficiency ; drug therapy

Calcium hydroxide (CH) is applied to improve disinfection of root canals in most root canal retreatment. This study aimed to analyze the CH removal efficacy using 7 different root preparing files (K file, pre-curved K file, EndoActivator, Ultrasonic file, pre-curved ultrasonic file, F file and needle irrigation alone) with apical transportation. Standardized models of curved canal with such apical transportation or not were set up before applying CH to root canal for 7 days. Seven techniques described above were used for its removal. Then the roots were disassembled and digital photos were taken. The ratio of residual CH in the overall canal surface was calculated using the image analyzer image pro plus 6.0. The data were analyzed using one-way ANOVA with post hoc Tukey test. Results revealed that CH was effectively removed (P<0.05) by using all 6 mechanical methods except irrigation alone. In curved root canals with apical transportation, EndoActivator, pre-curved ultrasonic file and F file were found to be more effective in removing CH than the other four file (P<0.001), while there was no significant difference among EndoActivator, pre-curved ultrasonic file and F file groups (P>0.05). The percentage of residual CH in the canal with apical transportation was higher than that in the canal without apical transportation (P<0.05). In conclusion, CH can be hardly removed completely. Canal with apical transportation will result in insufficient CH removal. EndoActivator, pre-curved ultrasonic file and F file are more effective in the curved root canal with apical transportation.

Objective To find out the importance of human bocavirus (HBoV) as an infectious agent for population in Beijing, China. Seroprevalence study was conducted by using expressed recombinant major capsid VP2 protein as an antigen.Methods Serum specimens collected from infants and children who visited the Children's Hospital Affiliated to the Capital Institute of Pediatrics for health check-up and adults visiting the Xuanwu Hospital, Beijing for diseases other than respiratory infections from April 1996 to March 1997 were used for the investigation. The major capsid protein VP2 from HBoV was expressed in E. coli strain BL21 (DE3) with the transformed PET30b vector inserted with full-length VP2 gene of HBoV and the specific antigenicity of this expressed protein was validated by previous study. Western blotting was used to detect specific IgG antibody against HBoV in collected serum specimens diluted to 1:200. Mock expressed protein was E. coli cells strain BL21 (DE3) with the transformed PET30b vector without insert. Anti-His monoclonal antibody and rabbit anti-HBoV VP2 polypeptides hyper-immune serum were used as positive control for antibody detection.Results Out of 677 serum specimens tested, 400 (59.1% ) were positive for HBoV by Western blotting. About 45.3% (34/75) of the newborns under 1 month of age had anti-HBoV antibodies, and antibody positive rates were decreased in age groups of 1 and 2 months (41.4% and 31.3%, respectively) then increased in the following ages from 6 months to 7 years old ( from 45.6% to 69.7% ). The antibody positive rates were maintained at a relatively constant level ( about 70% ) in the age groups from 7 years to 40 years of age and became lower ( 61.8% - 62. 8% ) in those over 50 years.Conclusions The high seroprevalence of antibody against recombinant HBoV VP2 protein and early age antibody acquisition indicate that HBoV has been circulating in population of Beijing, China as early as in 1996 and most of children had been exposed to HBoV by the age of 7 years. Infants under the age of 6 months were susceptible to this virus.

OBJECTIVETo explore the diagnostic value of 3D-indirectmagnetic resonance (MR) arthrography in detecting meniscustears of the knees.

METHODSForm January 2013 to January 2014, routine plain MR of the knees followed by the 3D-indirect MR arthrography was performed in 42 patients with suspected meniscal tears clinically. There were 31 males and 11 females, with an average age of 38.4 years old (ranged, 21 to 67 years old). The duration of the course ranged from 2 h to 15 d. The clinical symptom was knee pain. All the patients got subsequently arthroscopic examination or operation. The sensitivity and specificity of routine plain MR and 3D-indirect MR arthrography were compared based on the results of arthroscopic examination or operation.

RESULTSThe signal intensity in the area of meniscal tears on image of 3D-indirect MR arthrography was obviously higher than that of routine plain MR. The sensitivity of 3D-indirect MR arthrography was 85.79% (87/102), while the routine plain MR was 52.94% (54/102), and the specificity improved from 67.78%(61/90) to 86.67%(78/90). The difference was statistically significant (χ2 = 25.90, P < 0.01; χ2 = 9.13, P < 0.01).

CONCLUSIONIn comparison with the routine plain MR findings, 3D-indirect MR arthrography demonstrates meniscus tears of the knee with the better sensitivity and specificity.

Adult ; Aged ; Arthrography ; methods ; Female ; Humans ; Imaging, Three-Dimensional ; methods ; Knee Injuries ; diagnosis ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Tibial Meniscus Injuries

OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).

METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.

RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.

CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.

Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism

OBJECTIVETo determine the mechanism of pseudo-tears of the lateral meniscus caused by the transverse geniculate ligament (TL) and the miniscofemoral ligament(MFL) and to investigate a method to differentiate pseudo-tears from true tear of the lateral meniscus.

METHODSForm June 2012 to February 2014, MR examinations of 72 knees (44 left knees and 28 right knees) without tear of the lateral meniscus verified by arthroscopy were performed in the sagittal and coronal plane. There were 41 males and 31 females in the group, with an average age of 33.7 years old (ranged from 25 to 61). The MR appearance of the TL and the MFL was carefully observed.

RESULTSThere existed fatty tissue in the gap between the TL and the anterior horn of the lateral meniscus and its central tendinous attachment. On the sagittal images, the fatty tissue formed a linear high-signal cleft between the TL and the anterior horn of the lateral meniscus. This might be mistaken as an oblique tear within the anterior horn of the lateral meniscus. It was called as pseudo-tears of the anterior horn of the lateral meniscus. In sagittal plane, the MFL was identified as a circle-like or short stick-like area of low signal intensity anterior or posterior to the posterior cruciateligament. Nevertheless, a belt-shaped area of low signal intensity from the posterior horn of the lateral meniscus to lateral facet of the medial femoral condyle was identified in the coronal plane. A linear area of high signal intensity between the MFL and the lateral meniscus was found in sagittal plane, which might be mistaken as an oblique tear within the posterior horn of the lateral meniscus. It was called pseudo-tears of the posterior horn of the lateral meniscus. The occurrence rate of the TL was 34.7% (25/72). The prevaleribe of pseudo-tears of the anterior horn of the lateral meniscus was 18 cases. The shape of the anterior horn of the lateral meniscus was regular, and the course of the pseudo-tears cleft was oblique. The occurrence rate of the MFL was 73.6% (53/72), which included the anterior MFL 23.6% (17/72), the posterior MFL 70.8% (51/72) and the two ligaments coexisted 16.7% (12/72). The prevalence of pseudo-tears of the posterior horn of the lateral meniscus was 25 cases. All observed pseudo-tears had either in posteroinferiorly oblique direction (19/25) or in vertical direction (6/25).

CONCLUSIONBased on the location and direction of pseudo-tears and observation in the continuous sagittal plane and the coronal plane, pseudo-tears is easily differentiated from the true tear of the lateral meniscus

Adult ; Female ; Humans ; Knee Injuries ; diagnostic imaging ; surgery ; Knee Joint ; diagnostic imaging ; surgery ; Magnetic Resonance Imaging ; Male ; Menisci, Tibial ; diagnostic imaging ; surgery ; Middle Aged ; Radiography ; Tibial Meniscus Injuries

We predicted the anti-hepatitis B virus (HBV) active components and mechanism of Salvia miltiorrhiza based on network pharmacology. The active components of S. miltiorrhiza were obtained through TCMSP, PubChem database and literature research. The potential targets of the active components and HBV infection were predicted by SwissTargetPrediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to construct a visual network of active component-disease target and perform topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID platform. The molecular docking of key components and core targets was carried out by AutoDock Vina software. We screened out a total of 38 active components and 178 disease-component overlapping targets. Enrichment analyses obtained 405 related GO items and 68 signaling pathways, such as T/B cell receptor signaling pathways, PI3K/AKT signaling pathway, and mTOR signaling pathway. According to the results of molecular docking, most characteristic components of S. miltiorrhiza (miltionone Ⅱ, miltirone, protocatechuic acid, lithospermic acid, protocatechualdehyde) showed good affinity with the key targets (PIK3CA, APP, STAT3,AKT1 and mTOR). Furthermore, the anti-HBV activity of lithospermic acid, the representative active component of S. miltiorrhiza, and its regulation on PI3K/AKT and mTOR signaling pathways were investigated in an HBV replicating mouse model. Animal welfare and experimental procedures follow the regulations of the Animal Ethics and Welfare Committee of Hubei University. The results showed that lithospermic acid significantly inhibited HBV DNA replication, reduced serum HBsAg and HBeAg levels, and decreased the phosphorylation protein expression levels of AKT and mTOR in liver, indicating that lithospermic acid might exert the anti-HBV activity by regulating PI3K/AKT and mTOR signaling pathways.

Objective:To evaluate the clinical efficiency and prognostic factors of autologous peripheral blood stem cell trans-plantation (APBSCT) in 30 cases of multiple myeloma (MM). Methods:Two of the 30 patients received the second treatment of APB-SCT because of relapse after the first treatment. Thus, a total of 32 case-times of APBSCT were studied. Combination chemotherapy was inducted regularly before APBSCT (11 patients used bortezomib as an induction drug), and chemotherapy combined with the G-CSF regimen was used to mobilize peripheral blood stem cells. Preconditioning was based on melphalan. Results:Mononuclear cells in harvest were 6.41 × 108/kg, and CD34+cells in harvest were 4.75 × 106/kg. The median times of neutrophil and platelet engraftment were 9.5 and 11 d, respectively. The complete remission (CR) and very good partial remission (VGPR) rates were 37.5%and 34.4%af-ter APBSCT, respectively. The median overall survival (OS) was 67.27 months in all patients, and the median progression-free survival (PFS) was 29.77 months. The median PFS rates were 29 and 20 months in the patients who achieved CR and PR, respectively, and the median PFS was not observed in the patients who achieved VGPR. Statistical differences in PFS were detected between the CR+VGPR and PR groups (P=0.025). The CR rates were 63.6%and 23.8%in the bortezomib (bortezomib-based chemotherapy) and non-bortezo-mib groups (P=0.034), respectively. The median OS and PFS were not obtained in the bortezomib group, whereas the median PFS was 22 months in the non-bortezomib group (P=0.045). Conclusion: MM patients treated with bortezomib-based chemotherapy followed by APBSCT had prolonged PFS. APBSCT can improve the response and survival of MM patients.