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.

Objective:To construct a DNA vaccine co-expressing the HBV compound multi-epitope antigen gene, the hIL-12 and the anti-HBV siRNA genes, and to express this DNA vaccine in HepG2 cells. Methods:The HBV multi-epitope antigen gene was designed and synthesized before it was fused with enhanced green fluorescent protein(EGFP) gene, and cloned into the multi-clone site(MCS) of the eukaryotic expression vector pVAX1. The expressinig units of hIL-12 and siRNA were cloned into the BspH I and Mlu I site of pVAX1 respectively. Then the recombinant plasmid pVAX1-siHBV-HB-EGFP-hIL12 was transiently transfected HepG2 cells. The expression of HBV compound multi-epitope gene was observed through EGFP report gene. The expression of hIL-12 was analyzed by ELISA and the effects of anti-HBV siRNA was confirmed with rtPCR . Results: The analysis of enzyme digestion and sequencing both demonstrated that the trible-expressing HBV DNA vaccine has been constructed successfully. The green fluorescent image was detected in the transfected cells which could confirm the expression of the multi-epitope antigen gene. The amount of hIL-12 secretion was 1289pg/ml in supernatant at 48h after transfection and 1712pg/ml at 72h after transfection. The mRNA amount of HBV S gene, which was the siRNA target, had been obviously knockdown. Conclusion: The DNA vaccine co-expressing the HBV compound multi-epitope antigen gene, the hIL-12 and the siRNA genes was constructed and transiently expressed in HepG2 cells, and siRNA had shown us a good anti-HBV effect. It laid a foundation of further study on anti-HBV effect of the new DNA vaccine.

OBJECTIVETo explore the clinical results of postoperative rehabilitation of patellar fracture by modified seated position of different knee flexion angles, thereby enrich the therapeutic tool of orthopaedics of traditional Chinese and western medicine and provide the evidences for refinement and modernization of traditional Chinese exercise therapy.

METHODSFrom January 2009 to June 2012,90 patients with patellar transverse fractures were treated with open reduction and internal fixation by tension band wire and rehabilitation exercises. There were 52 males and 38 females, aged from 21 to 77 years old with an average of 50.0 years old. Three methods of rehabilitation exercises were adopted in the patients after fractures clinical union. There were 21 males and 14 females in group A (trained by modified seated position of knee flexion about 60 degree), 21 males and 14 females in group B (trained by modified seated position of knee flexion about 30 degree), 10 males and 10 females in group C (trained by walk). The rehabilitation-training time was 1 month. Fracture healing informations were observed by X-ray films. The Böstman patellar fracture function scores were compared before and after training among three groups.

RESULTSPostoperative follow-up time was 6 months. All fractures obtained bone union and the average healing time was 3 months (ranged,2 to 4 months). Böstman patellar fracture function scores in group A, B, C before training were 18.89 ± 2.19, 18.74 ± 2.03, 18.85 ± 2.92, respectively; there was no significant differences in among three groups (P > 0.05). After training, Böstman patellar fracture function scores in group A, B, C were 29.40 ± 1.14, 26.09 ± 3.86, 25.70 ± 4.09, respectively; group A was highest than other two groups; and there was no significant differences between group A and group B.

CONCLUSIONModified seated position of knee flexion about 60 degree was practical and effective training in postoperative rehabilitation for the treatment of patellar fracture, it can obtain the better clinical results than other training method such as walk or modified seated position of knee flexion about 30 degree.

Adult ; Aged ; Case-Control Studies ; Female ; Fracture Fixation, Internal ; methods ; Fracture Healing ; Fractures, Bone ; rehabilitation ; surgery ; Humans ; Male ; Middle Aged ; Patella ; injuries ; surgery

Objective To evaluate the feasibility of 3-(4-~(18)F-fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno [3,4-c]pyridin-5-one ( is F-FDTP) as a potential dopamine D4 receptor PET imaging agent.Methods ~(18)F-FDTP solution in ethanol-physiological saline was incubated with calf serum to test its in vitro stability through the determination of radiochemical purity.Normal rats were injected intravenously with ~(18)F-FDTP and then sacrificed at 2,5,10,15,30,60 and 120 min after anesthesia.Blood,organs and brain tissue samples were collected.All samples were weighed and measured for radioactivity.The uptake of samples was expressed as percentage activity of injection dose per gram of tissue ( % ID/g).Results The stability of ~(18)F-FDTP was satisfactory and its radiochemical purity was above 95% after incubation 120 min at 37℃ in calf serum.The biodistribution showed that ~(18)F-FDTP could penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal certex,hippocampus,cerebellum,where the D_4 receptor was reportedly located.The radioactivities in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum,pons were (0.42±0.03),(0.46±0.05),(0.54±0.04),(0.39±0.04),(0.45±0.06),(0.35±0.04) %ID/g,respectively,2 min post injection.And there was difference between the normal biodistribution results and the blocking experimental results:(0.36 ±0.05),( 0.33±0.05 ),(0.55±0.05 ),(0.30±0.07 ),(0.34±0.07 ) and (0.32±0.04) % ID/g in hippocampus,hypothalamus,striatum,frontal cortex,cerebellum and pons,respectively.Conclusions ~(18)F-FDTP can penetrate through the blood-brain barrier and selectively accumulate in striatum,hypothalamus,frontal cortex,hippocampus,cerebellum,where the D_4 receptor was known to concentrate.These preliminary results suggest that ~(18)F-FDTP is a potential dopamine D_4 receptor imaging agent and further studies are needed.

OBJECTIVEThe Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL.

METHODSA total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

RESULTSToxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality.

CONCLUSIONSThe drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Asparaginase ; adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction

OBJECTIVE: To investigate the optimal doses of X-ray irradiation and plasmid injection in the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo. METHODS: We observed the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy with different doses of X-ray irradiation (2, 10, 20 Gy) and plasmid injection (10, 20, 30 microg) in nude mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in tumor by RT-PCR. RESULTS: The tumor growth rate of the nude mice irradiated locally with 20 Gy X-rays after the plasmid injection was significantly lower (P < 0.05 ) than that of the nude mice irradiated locally with 2 Gy or 10 Gy X-ray 3 days after the irradiation. The tumor growth rate of the nude mice injected locally with 20 microg or 30 microg plasmid was significantly lower (P <0.05 ) than that of the nude mice injected locally with 10 microg plasmid. Both pcDNA3. 1-Egr. 1p-p16 group and pcDNA3. 1-Egr. 1p-p16 +20 Gy group had p16 mRNA expression, but the mRNA level of pcDNA3. 1-Egr. 1p-p16 +20 Gy group was higher than that of pcD- NA3. 1-Egr. 1p-p16 group. CONCLUSION In the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation was 20 Gy and the optimal dose of plasmid injection was 20 microg. The anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 combined with radiotherapy is better than that of radiotherapy or gene therapy alone, which may be related with the enhanced p16 expression in tumor after the irradiation.
Animals ; Combined Modality Therapy ; DNA ; genetics ; Early Growth Response Protein 1 ; genetics ; Female ; Genes, p16 ; Genetic Therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Pancreatic Neoplasms ; radiotherapy ; therapy ; Recombinant Proteins ; metabolism

OBJECTIVETo observe the curative effects of post-stroke hand dysfunction treated with acupuncture at Zhongzhu (TE 3) and Waiguan (TE 5).

METHODSSixty cases of post-stroke hand dysfunction were randomly divided into an observation group (30 cases) and a control group (30 cases). Routine medicine, physical therapy, occupational therapy and other rehabilitation trainings were applied in both groups; Zhongzhu (TE 3) and Waiguan (TE 5) were punctured in observation group. Scores of nervous functions deficit by the National Institutes of Health Stroke Scale (NIHSS), hand function, walking ability, activities of daily living (ADL) by Modified Barthel Index Scale were e valuated in both groups before and after treatment.

RESULTSAfter treatment, the scores of hand function, walking ability, ADL and NIHSS were improved in both groups (all P < 0.01), and the hand function, walking ability and ADL in observation group were superior to those in control group (all P < 0.05).

CONCLUSIONRoutine medicine and rehabilitation trainings combined with acupuncture at Zhongzhu (TE 3) and Waiguan (TE 5) to treat post-stroke hand dysfunction can obviously improve the hand dysfunction after stroke, enhance the abilities of walking and daily living, and increase the curative effect.

Activities of Daily Living ; Acupuncture Therapy ; Aged ; Female ; Hand ; physiopathology ; Humans ; Male ; Middle Aged ; Stroke ; physiopathology ; therapy ; Walking

We have developed a novel silicon microchannel system for the research of the red blood cell rheology and deformation. Recurring to many kinds of information technologies and advanced test means such as the electronic microscope, the image acquisition system and the computer processing system and by using the up-to-date Micro Electro Mechanical System (MEMS) technology, a new measuring system of red bood cell deformation is designed based on the chip and a model using the silicon microchannel to simulate capillary vessel network. It provides a real-time collection and anaysis of data which include image, speed, flow parameter, and so on. It provides printing, storage of the analysis results and patients' database management.
Computers ; Equipment Design ; Erythrocyte Deformability ; Erythrocytes ; physiology ; Hemorheology ; instrumentation ; Humans ; Image Processing, Computer-Assisted ; instrumentation ; methods ; Information Storage and Retrieval ; methods ; Silicon ; Software

OBJECTIVETo investigate the hepatotoxic effects of N, N-dimethylformamide (DMF) in the workers of a synthetic leathers factory, and the effects on liver function of covariates such as alcohol consumption and other factors.

METHODSThe workers were classified into three groups (low, high and the control) by the concentration of DMF in workplace which was determined in the past two years. A questionnaire was drawn up for relevant demographic characteristics and other factors influencing liver function. The bloods were collected for laboratory test which included parameters especially relevant to the liver (ALT AST and gamma GT).

RESULTSLow and high-exposure groups were significantly associated with elevated ALT and gamma GT, and high-exposure group was significantly associated with elevated Liver index. Modeling by stepwise regression analysis demonstrated that high concentration of DMF and BMI were associated with and elevated ALT, gamma GT and Liver index, besides DMF and BMI, the elevation of ALT was also associated with high TRIG. AST was only associated with alcohol consumption. The AST/ALT ration < 1 was present in 86.7% of the exposure workers of liver function abnormal.

CONCLUSIONDMF can cause liver function alternations even if air concentration of DMF was below PC-TWA. Besides the levels of DMF exposure, obesity (BMI) and alcohol consumption are covariates alternating liver function. Liver index can be a parameter for assessment liver function, and the AST/ALT ration < 1 may serve as markers of risk in health screening programs.

Adult ; Alanine Transaminase ; blood ; Dimethylformamide ; toxicity ; Female ; Humans ; Liver ; metabolism ; physiopathology ; Liver Function Tests ; Male ; Occupational Exposure

OBJECTIVETo investigate abnormal liver function associated with polymorphism of GSTT1, GSTM1 and CYP2E1 in workers exposed to N, N-dimethylformamide.

METHODSSixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case. One hundred and twenty five control subjects with similar work tasks were selected from the same factory. Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR, and for CYP2E1 PstI by PCR-RFLP assay.

RESULTSThe frequency of positive GSTM1 was 59.42% in cases and 38.40% in control, with an odds ratio (OR) of 2.34,95% CI: 1.29-4.29 (P=0.005). For GSTT1 and CYP2E1 PstI, the frequencies of genotypes showed no significant difference between case and control.

CONCLUSIONGSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N, N-dimethylformamide.

Adult ; Chemical and Drug Induced Liver Injury ; etiology ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Dimethylformamide ; adverse effects ; Female ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Occupational Exposure ; adverse effects ; Polymorphism, Genetic