Currently, the resistance of first-line anti-tuberculosis drugs has made the prevention and treatment of tuberculosis increasingly difficult, posing a serious threat to global public health. Several studies have shown that efflux pumps are one of the important causes for bacteria to develop multi-drug resistance and extremely-drug resistance, and efflux pump inhibitors can inhibit the efflux of antibacterial drugs, thereby reducing bacterial drug resistance. Numerous natural products and synthetic compounds have been reported to possess efflux pump inhibitory activity, but they have not been applied in clinical settings because of their toxicity, pharmacokinetic properties, etc. Therefore, we summarized the efflux pump inhibitory activity, antimicrobial activity, and structure-activity relationships of reported efflux pump inhibitors against Mycobacterium tuberculosis in recent years, providing references for the development of new efflux pump inhibitors with better activity and lower toxicity.

For screening the potential drugs as anti-liver fibrosis candidates, we established a high- throughput drug screening cell model based on COL1A1 promoter. The activity of COL1A1 promoter and luciferase reporter gene can be elevated by TGF-β1, and inhibited by candidate drugs. We constructed a recombined plasmid with COL1A1 promoter and luciferase reporter gene pGL4.17, the activity of COL1A1 promoter was reflected by fluorescence intensity. COL1A1 promoter activity was detected by Dual-Luciferase Reporter Assay System, it came that the relative luciferase activity of COL1A1 promoter was 15.98 times higher than that of control group induced by TGF-β1, showing the recombined plasmid could be used in cell model. The recombined plasmid was transfected into human hepatic stellate cells LX2, detected the effect of potential drugs, and obtained a stable expression system through stable transfection and monoclonal cell culture. A sample which could reduce COL1A1 promoter activity signally by our cell model, decreased collagen I mRNA and protein expression detected by real-time RT-PCR and Western blotting. It indicates this novel cell model can be used in high-throughput drug screening of potential anti-liver fibrosis drugs.
Collagen Type I ; genetics ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; Hepatic Stellate Cells ; High-Throughput Screening Assays ; Humans ; Liver Cirrhosis ; drug therapy ; Luciferases ; Plasmids ; Promoter Regions, Genetic ; RNA, Messenger ; Transfection ; Transforming Growth Factor beta1 ; pharmacology

Objective To design a new type of field operation instrument for easy to spread a rescue surgery rapidly in field first -aid at the present stage. Methods The traditional field operation instrument set is innovated in its composition, structure and function. The packing instrument procedure can be omitted. The new field operation instrument set is made of four different operation instrument boxes, two of which can be put into a standard field medical case. Results It is designed to be convenient to have a rescue surgery rapidly and to be washed, sterilized, conveyed and kept in aseptic storage. Conclusion The new field operation instrument case has such advantages as compactness, reasonable allocation and function completed, so it can be used easily.

mRNAs of alpha-adrenoceptor (α-AR) subtypes are found in neurons in dorsal root ganglion (DRG) and change after peripheral nerve injury. In this study, the distribution of α-AR subtype proteins was studied in L5 DRG of normal rats and rats with chronic constriction injury of sciatic nerve (CCI). Using immunofluorescence technique, it was found that α1A-, α1B-, and α2A-AR proteins were expressed in large, medium, and small size neurons in normal DRG, and significantly increased in all size neurons 14 days after CCI. α1D- and α2C-AR was also expressed in all size neurons in normal DRG. However, α1D-AR was significantly increased and α2C-AR was decreased in small size neurons 14 days post CCI. α2B-AR neurons were not detectable in normal and CCI DRG. Co-expression of α1A- and α2A-AR in the same neuron was observed in normal DRG and increased post CCI. Collectively, these results indicated that there is distinct distribution of α-AR subtypes in DRG neurons, and the distribution and levels of expression of α-AR subtypes change differently after CCI. The up-regulation of α-AR subtypes in DRG neurons may play an important role in the process of generating and transmitting neuropathic pain.

Objective To investigate the role of acid and bile reflux in children with gastroesophageal reflux disease (GERD) and to evaluate the significance of detecting acid and bile reflux in diagnosing GERD in children.Methods Using ambulatory 24 h pH mo-(nitoring) and bilirubin monitoring technique, we simultaneously assessed the changes of intraesophageal pH and bile reflux in 23 subjects (including 11 healthy controls and 12 patients with GERD).Results The time of esophageal acid exposure (pH

OBJECTIVETo observe the effect of Qubi Recipe (QR) on the expression of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and hypoxia-inducible factor (HIF)-1alpha in rats with type II collagen-I induced arthritis (CIA), and to explore its therapeutic roles and mechanism.

METHODSTotally 72 male SD rats of SPF grade were recruited. Twelve were randomly selected as the blank control group. The CIA model was established in the rest 60 rats by subcutaneously injecting type II collagen of bovine emulsion from the tail root and induction of incomplete Freund's adjuvant. On day 15 after primary immunization rats were randomly divided into four groups, i.e., the CIA model group, the Tripterygium Glycosides (TG) group (at the daily dose of 9.68 mg/kg body weight), the high dose QR group (at the daily dose of 6.66 g/kg body weight), and the low dose QR group (at the daily dose of 3.33 g/kg body weight), 15 in each group. Corresponding medication was given to rats in all groups by gastrogavage once daily for 4 successive weeks. An equal volume of pure water was given to rats in the blank control group and the CIA model group by gastrogavage, once daily for 4 successive weeks. The swelling degree of the joints was measured. Rats were sacrificed after 4-week treatment. Plasma levels of SOD, MDA, and GSH-Px were measured with colorimetric method. The expression of HIF-1alpha was detected by immunohistochemistry.

RESULTS(1) Compared with the CIA model group, the swelling degree of the joints was significantly alleviated in the TG group and the high dose QR group (P < 0.01, P < 0.05), and it was obviously milder in the high dose QR group than in the TG group (P < 0.05). (2) Compared with the CIA model group, the activities of GSH-Px could be obviously elevated and activities of MDA lowered in the TG group, the high dose QR group, and the low dose QR group (P < 0.05). Plasma activities of SOD could be obviously elevated in the high dose QR group and the TG group (P < 0.05). (3) Compared with the CIA model group, the expression of HIF-1alpha obviously decreased in the TG group and the high dose QR group (P < 0.05), and it showed a decreasing tendency in the low dose QR group with no statistical difference (P > 0.05).

CONCLUSIONSQR could markedly alleviate the swelling degree of ankle joints in CIA model rats. Its therapeutic efficacy was superior to that of TG. Its mechanism might be achieved through down-regulating expression of HIF-1alpha in the joint, and regulating activities of SOD, MDA and GSH-Px in the plasma.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; blood ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Joints ; metabolism ; pathology ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; blood

OBJECTIVETo detect the expressions of human epidermal growth factor receptor 2 (Her-2), epidermal growth factor receptor (EGFR), presenilin 2 (PS-2) and estrogen receptor (ER) in breast cancer and discuss their clinical implications.

METHODSThe expressions of Her-2, EGFR, PS-2 and ER were measured immunohistochemically in 108 patients with breast cancer.

RESULTSThe positive expression rates of Her-2, EGFR, PS-2 and ER were 37.0%, 40.7%, 57.4% and 53.7% respectively in the breast cancer patients. The expression of Her-2 was not correlated with EGFR, but inversely correlated with PS-2 and ER. The expressions of Her-2 and EGFR, PS-2, ER were correlated with the histological grades (P<0.05), and Her-2, EGFR and ER expressions with lymph node metastasis (P<0.05). The expressions of Her-2, EGFR, PS-2 and ER did not correlate to the pathological types, patient's age and tumor size (P>0.05).

CONCLUSIONExpressions of Her-2 and EGFR often suggests an unfavorable prognosis while expressions of PS-2 and ER suggest a more favorable one. Expressions of Her-2, EGFR, PS-2 and ER are useful prognostic factors in breast cancer patients.

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Presenilin-2 ; biosynthesis ; Prognosis ; Receptor, Epidermal Growth Factor ; biosynthesis ; Receptor, ErbB-2 ; biosynthesis ; Receptors, Estrogen ; biosynthesis

OBJECTIVETo evaluate the immunostimulatory capacity of human peripheral blood dendritic cells (DCs) with Her2/neu gene transfection mediated by adeno-associated virus.

METHODSThe HLA genotypes of the breast cancer cells SK-BR-3 and MCF7 were determined, and the mononuclear cells from healthy donors with matching HLA genotype were isolated by Ficoll-Hypaque density gradient separation. The isolated cells were divided into two groups with or without transfection with the recombinant virus harboring Her2/neu gene. The cells were cultured for 7 days in RPMI 1640 medium supplemented with 10% AB human serum, GM-CSF, interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). The mature DCs were then harvested from the cell culture and their phenotypes were identified using flow cytometry. MTT assay was employed to examine the specific killing activity of the T cells induced by the DCs.

RESULTSThe DCs transfected with the recombinant adeno-associated virus expressed CD1a, CD86 and CD83 at the rate of 98.10%, 99.42%, and 84.59%, and those without the viral transfection expressed the markers at the rate 92.69%, 98.07%, and 82.72%, respectively, showing no obvious differences in the phenotypes of the two DCs. The transfected DCs, however, showed markedly higher expression rates of CD40 and CD80 than the non-transfected DCs (61.02% vs 36.19%, and 97.61% vs 55.5%, respectively). The DCs, irrespective of the transfection, showed comparable capacities in stimulating T cell proliferation. The transfected DCs exhibited the capacity of inducing the T cells to specifically kill the target tumor cells, with the highest killing rate of (39.7-/+7.2)%.

CONCLUSIONThe immunostimulatory capacity of human peripheral blood DCs are enhanced by Her2/neu gene transfection mediated by adeno-associated virus.

Breast Neoplasms ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; metabolism ; Dependovirus ; genetics ; metabolism ; Genes, erbB-2 ; genetics ; Genetic Vectors ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Leukocytes, Mononuclear ; cytology ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Recombinant Proteins ; genetics ; immunology ; metabolism ; Transfection

To establish a rat model of rheumatoid arthritis (RA) with kidney deficiency syndrome.

OBJECTIVETo summarize methods for repair of claw hand deformity after burn.

METHODSNinety-seven patients with 136 claw hands after burn hospitalized from May 1992 to May 2007 were repaired with skin grafting (104 hands) and transposition of skin flap (32 hands), among which 21 hands were minor-grade, 92 hands moderate, 23 hands severe. The metacarpophalangeal joint was repaired after scar release in dorsum of hand with manual extraction reduction, release of collateral ligament and joint capsula, separation of adhesion in joint, tendon lengthening for obvious contracture. Restitution of finger flexion deformity, lysis of adhesion and grafting among first web and finger webs, repair of central slip extensor tendon or phalangeal arthrodesis were performed according to the abnormal condition after lysis of dorsal scar of hand. The metacarpophalangeal joint from 31 patients were not repaired with above methods for severe finger flexion deformity, their palmar scar were loosened and transplanted firstly, then scar in dorsum of hand were loosened, metacarpophalangeal joint were repaired, flap or skin were transferred or transplanted. General rehabilitation were performed routinely after operation.

RESULTSThe ending of flaps (4 hands) due to the scar were necrosis after transposition and healed through dressing change, other skins or flaps all survived. Most articular deformities were corrected completely or basically. Functions including palmar opposition, grasp were also recovered with satisfactory results.

CONCLUSIONSkin transplantation and transferring of skin flap with overall planning and individual isatin are the key points for repair of claw hand after burn.

Adolescent ; Adult ; Burns ; complications ; Child ; Child, Preschool ; Cicatrix ; etiology ; surgery ; Female ; Hand Deformities, Acquired ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps ; Young Adult