Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg.kg-1 per day) and the high dose of BR combined with glycyrrhetinic acid (GA, 25 mg.kg-1 per day) or liquiritin (LQ, 20 mg.kg-1 per day) for 7 consecutive days. Compared with the control, brucine caused 24.5% and 34.6% decrease of CYP3A-associated testosterone 6beta-hydroxylation (6betaTesto-OH) and CYP2C-associated tolbutamide hydroxylation (Tol-OH), respectively, and 146.1% increase of CYP2El-associated para-nitrophenol hydroxylation (PNP-OH) at the high dose level. On the other hand, (BR+GA) caused 51.4% and 33.5% decrease, respectively, of CYP2El-associated PNP-OH and CYP1A2-associated ethoxyresorufin-O-de-ethylation (EROD) as compared with the high dose of BR group. Meanwhile, (BR+LQ) caused 41.1% decrease of CYP2El-associated PNP-OH and 37.7% increase of CYP2C-associated Tol-OH. The results indicated that the co-administration of BR with GA or LQ had effect on mRNA expression and activities of the CYP450 enzymes mentioned above to some extent, and the in vivo antagonism of LQ on BR-induced CYPs adverse effects and the in vivo inhibitory action of GA on CYP2E1 and 1A2 might play an important role in the detoxification of Radix Glycyrrhizae against Strychnos nux-vomica L.

OBJECTIVE:To establish a method for determining recombinant human calmodulin B subunit(rhCNB)in rat plas-ma,and study its pharmacokinetics characteristics. METHODS:ELISA double-antibody sandwich method was adopted. 1 μg/ml rhCNB monoclonal antibody mAb was wrapped,added to the to-be-test sample,rhCNB polyclonal antibody pAb(dilution ratio of 1∶5 000)and HRP-labeled conjugate of anti-IgG(dilution ratio of 1∶10 000)were added. Using tetramethylbenzidine for develop-ing,microplate reader was conducted in wavelength of 450 nm to determine the absorbance value(OD value)and plasma concen-tration of 6 rats after 2,15,30,60,120,240,480,720 min of iv 2.5 mg/kg rhCNB,and the pharmacokinetic parameters were calculated by BAPP 3.0 software. RESULTS:The linear range of rhCNB were 0.195-12.5 ng/ml(r2=0.995 0),lower limit of quan-titation was 0.195 ng/ml,accuracy were 97.300%-103.622%(RSD<7.5%,n=6);RSDs of within-batch,inter-batch,freezing and thawing 3 times were no higher than 8.5%(n=6,18,15). rhCNB pharmacokinetics characteristics in rat fitted to two-com-partment model,AUC0-720 min was 173.038 mg·min/L and t1/2 was 94.62 min. CONCLUSIONS:The established method has high specificity and sensitivity,good accuracy and precision,which can be used for rhCNB quantitative detection and pharmacokinetics study in biological samples.

Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes. Purified flammulin emulsified with Freund's adjuvant was injected subcutaneously into New Zealand white rabbits. After several immune enhancements, these animals were bled and sera were separated. Antiserum against flammulin in Western blots were applied to determine if flammulin be present in the liquid state culture or fruiting body. The result showed that anti-flammulin serum could recognize the aqueous extract of fruiting body in SDS-PAGE gels under the reducing conditions, no flammulin was detected in mycelia of Flammulina Velutipes.

OBJECTIVETo explore an ideal method for repairing the skin-soft tissue defects according to the different anatomical units of cheek, and find reasonable design principles to transfer the expanded flaps.

METHODSAccording to the location of the defect, we placed 1-3 appropriate expanders nearby, when the flap expanded enough we adopted advanced skin flaps, rotation-advanced skin flaps or transposition skin flaps to repair the defect. In this group of 269 cases, the defects were secondary to hemangioma, various scars, nevus or nevus excision.

RESULTSIn all 269 cheek defects, 305 expanded flaps were developed which included 145 rotation-advanced flaps, 121 advanced skin flaps and 39 transposition skin flaps. 52 of them generated complications, including blood circulation disorder of the distal part of flaps, hematoma, infection, injection, lower eyelid ectropion, expander extrusion and capsule contracture. Mostly, these complications didn't affect the final results.

CONCLUSIONSThe principles presented in this article are the guidelines to treat the skin-soft tissue defect of check with tissue expansion. The satisfied results come from the reasonable flap designs.

Adolescent ; Adult ; Cheek ; surgery ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Surgical Flaps ; Tissue Expansion ; methods ; Young Adult

Alzheimer’s disease (AD) remains to be a grand challenge for the international commu-nity despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripo-tent cells (iPSCs). Comprehensive information collection, better understanding of the disease mech-anisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

OBJECTIVETo study the effects of drug plasma of musk and olibanum (DP-M&O) on the release of inflammatory cytokines from monocytes and the expressions of the proteins associated with inflammation of prostatic or endothelial cells induced by prostate antigen (PAg) stimulation.

METHODSWe prepared DP-M&O using SD rats and monocytes and PAgs using BALB/c mice. We pre-treated the monocytes with DP-M&O at the gradient concentrations of 0, 2.5, 5, 10, and 20% for 1 hour, activated them with PAgs, and then cultured them for 96 hours, followed by detection of the release of inflammatory cytokines. We co-cultured the prostate RWPE-1 cells with the endothelial EA. hy926 cells, pre-treated them with the same gradient concentrations of DP-M&O as above for 1 hour, activated with PAgs, and cultured for 96 hours. Then we determined the expression levels of the proteins associated with inflammation of RWPE-1 and EA. hy926 cells by Western blot.

RESULTSDP-M&O decreased the levels of TNF-alpha, IL-1beta, IL-6, and IL-8 and increased that of IL-10 in a concentration-dependent manner. Significant differences were found between the 20% P-M&O and PAg groups in the release of the inflammatory cytokines TNF-alpha (70.8 +/- 22.3 vs. 277.1 +/- 65.5, P < 0.01) , IL-113 (277.5 +/- 22.6 vs. 630.4 +/- 89.7, P <0.01), IL-6 (232.7 +/- 62.7 vs. 994.2 vs. 182.3, P < 0.01), IL-8 (227.3 +/- 79.2 vs. 769.3 +/- 284.1, P < 0.01), and IL-10 (640.2 +/- 201.2 vs. 271.1 +/- 55.8, P < 0.01). Compared with the PAg group, the 10 and 20% P-M&O groups showed remarkable decreases in the protein expression of MCP-1/CCL2 in the RWPE-1 cells (1.12 +/- 0.34 vs. 0.56 +/- 0.11 and 0.34 +/- 0.08) and that of VCAM-1 in the EA. hy926 cells (0.94 +/- 0.22 vs. 0.52 +/- 0.17 and 0.38 +/- 0.12) (P < 0.05 or 0.01).

CONCLUSIONThe compatibility of musk and olibanum can decrease the expression of MCP-1/CCL2 in prostate cells and VCAM-1 in vascular endothelial cells, blocking the adhesion of leucocytes and suppressing inflammatory response.

Animals ; Blotting, Western ; Cytokines ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Fatty Acids, Monounsaturated ; pharmacology ; Frankincense ; pharmacology ; Inflammation ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; Male ; Mice ; Mice, Inbred BALB C ; Monocytes ; drug effects ; metabolism ; Prostate ; cytology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Circular RNA (circRNA) is a new type of non-coding RNA with closed circular structures that are widely distributed in various tissues Compared with traditional linear RNA, circRNA does not have 5′ and 3′ ends and will not be easily degraded by exonuclease It can stably exist in a variety of body fluids and is evolutionarily conserved It has become a key research object of clinical non-coding RNA Malignant tumors have the characteristics of late detection, rapid progression, and easy recurrence Currently, effective treatment methods are lacking, and their morbidity and mortality have been high Therefore, how to carry out early diagnosis, treatment intervention and prognosis evaluation is one of the research frontier of contemporary medical research CDR1as is the most widely studied circRNA It can regulate the expression of downstream genes through sponge microRNA (miRNA) or directly bind to RNA-binding proteins (RBPs) to activate related signaling pathways, thereby promoting or inhibiting tumor progression, and even affecting tumor chemotherapy sensitivity CDR1as mainly exists in the cytoplasm and can be released into the blood at the early stage of the disease Therefore, CDR1as may become a bi-omarker for early diagnosis of malignant tumors or an ideal target for therapeutic intervention Focusing on the characteristics and biological functions of circRNA, this article reviews the expression level, mechanism of action and related signaling pathways of CDR1as in the occurrence and development of malignant tumors At the same time, this article analyzes the current research status of CDR1as, preliminarily summarizes the problems it may face in clinical applications in the future, and puts forward ideas and suggestions on the future research direction of CDR1as

OBJECTIVETo explore the effect and mechanism of Poly I:C in inducing growth inhibition and apoptosis of human hepatocellular carcinoma SMMC-7721 cells.

METHODSSMMC-7721 cells were treated with different doses of Poly I:C for 24, 48, and 72 h, and the cell growth inhibition rate was analyzed with CCK-8 assay. The cell cycle and the apoptosis were analyzed using flow cytometry with Annexin-V and PI staining, and quantitative RT-PCR analysis were used to detect the expression of TLR3, TRIF, and IFN-beta mRNA in cells.

RESULTSIn the cells exposed to Poly I:C at low, moderate, and high doses, the inhibitory rates was the highest in high-dose Poly I:C group, and at a given Poly I:C dose, prolonged exposure resulted in significantly increased cell growth inhibition rate (P<0.05). Flow cytometry showed that Poly I:C induced cell apoptosis in a time- and dose-dependent manner and significantly increased the percentage of G1-phase cells as compared with that in the control group. The mRNA level of TLR3, TRIF, and IFN-beta were also increased following Poly I:C treatment in comparison with the control group.

CONCLUSIONPoly I:C can induce significant growth inhibition and apoptosis of SMMC-7721 cells in a dose- and time-dependent manner possibly by causing cell cycle arrest and TLR3 signaling pathway activation that leads to IFN-beta production and cell apoptosis.

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Interferon-beta ; genetics ; metabolism ; Liver Neoplasms ; pathology ; Poly I-C ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Receptors, Cholecystokinin ; metabolism ; Signal Transduction ; Toll-Like Receptor 3 ; genetics ; metabolism

OBJECTIVETo find a way to having higher bond strength on mottled enamel.

METHODSSixty mottled enamel first bicuspid teeth extracted from fifteen patients needing orthodontic force were prepared and divided into four groups. Group A was routine acid etched, group B was air abraded, group C was etched by clearfil liner self-etching primer, group D was air abraded and then etched by clearfil liner self-etching primer. Next the bond and resin were used. The shear bond strength was observed and compared. The data were analysed by SPSS 11.5 statistical package.

RESULTSThe shear bonding strength of group A was (2.247 +/- 0.261) MPa, group B was (5.374 +/- 0.469) MPa, group C was (4.345 +/- 0.401) MPa, group D was (5.791 +/- 0.636) MPa. The strengths of four groups were significantly different (P < 0.01). The adhesive remnant index (ARI) scores of the four groups had no significant difference.

CONCLUSIONIn clinic, using air abrasion surface preparation technique is an acceptable way to enhancing the shear bond strength before sticking the orthodontic bonding on dental fluorosis.

Acid Etching, Dental ; Dental Bonding ; Dental Stress Analysis ; Fluorosis, Dental ; Humans ; Orthodontic Brackets ; Resin Cements ; Shear Strength

OBJECTIVETo investigate the feasibility of utilizing self-designed score system for lower lumbar vertebral burst fractures to select surgical approach.

METHODSFrom January 2006 to December 2011, the clinical data of 56 patients with lower lumbar vertebra burst fractures who underwent surgical treatment were retrospectively analyzed. There were 42 males and 14 females with an average age of 43.1 years old (ranged, 19 to 65). Causes of injury included falling down (40 cases), traffic accidents (12 cases), and crashing injury by heavy objects(4 cases). Injury site was L3 in 37 cases, L4 in 16 cases, and L5 in 3 cases. According to the AO classification, 17 cases were type A3.1, 14 cases were type A3.2, 25 cases were type A3.3. According to Frankel grade of nerous function, 2 cases were grade B, 5 cases were grade C, 9 cases were grade D and 40 cases were grade E. Surgical methods and approaches were chosen based on the comprehensive evaluation of AO classification, condition of posterior column injury and spinal canal encroachment. Surgical methods and approaches included trans-vertebra fixation (15 cases), intra-vertebra pedicle screw fixation (21 cases), combination of anterior and posterior approaches (11 cases), one-stage posterior approaches (9 cases). Cobb angles, restorations of the affected vertebral anterior border height, and conditions of spinal canal encroachment were compared before and after surgery. Conditions of bone graft fusion and internal fixation (if bending, loosening or breakage existed) were observed. Spinal cord functions were assessed according to Frankel grade. Localized pain and working status of patients were also assessed at the last follow-up.

RESULTSNo incision infection was found and no spinal nerve symptoms improved in all of 56 patients. All patients were followed up for 12 to 60 months with a mean of 28.5 months, without internal fixation loosening or breakage. There was significant differences in Cobb angle, vertebral anterior border height and recovery of spinal canal encroachment between preoperative and postoperative instantly (P < 0.05), however, there was no significant difference between postoperative instantly and final follow-up (P > 0.05). Thirteen cases obtained fusion by trans-vertebra fixation, 20 cases obtained fusion by intra-vertebra fixation, and 20 cases were treated by the combination of anterior and posterior approaches or one-stage posterior approaches all of patients obtained fusion. Spinal nervous function recovered I to II grade, 1 case was grade C, 3 cases were grade D, 52 cases were grade E. Localized pain was assessed as P1 in 52 cases, P2 in 3 cases, and P3 in 1 case. Working status was classified into W1 in 12 cases, W2 in 39 cases, and W3 in 5 cases.

CONCLUSIONThe lower lumbar vertebra and thoracolumbar junction exhibit different injury characteristics due to variations in anatomy and biomechanics. A comprehensive score of the AO classification, posterior column injury and degree of spinal canal encroachment will guide the selection of surgical method and approach for the treatment of lower lumbar vertebra burst fractures.

Adult ; Aged ; Biomechanical Phenomena ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Spinal Fractures ; surgery ; Spinal Fusion ; methods