This paper introduces the development and application of health-related quality of life (HRQOL) scales in research on coronary heart disease (CHD). Currently, the scales for CHD patients have been more systematically developed and widely used in foreign countries, while domestically in China, they are developed successfully but problematically; research in this field has started later and the scales introduced are limited and not suitable for the entire range of domestic CHD patients. Thus, this paper introduces 26 HRQOL scales in research on CHD, including five generic scales, ten disease-specific scales from abroad and eleven scales originating from China. With the deficiency of HRQOL scales, especially that in traditional Chinese medicine and specific scales, this paper analyzes and summarizes the problems existing in development of scales. The authors also provide solutions in order to help the development and application of scales in further studies.

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

To explore the relationship of mieroglia activation,motoneuronal loss in the ventral horn of spinal cord and sciatic nerve regen-eration after the sciatic nerve injury,Sprague-Dawley rats were prepared a modal of the fight sciatic nerve crash injury.The immunoreactiv-ity(-ir)ofmicroglia and number of the motoneurons inthe ventral horn of spinal cord were detected at 3 and7 days,light and electron mi-croscopic detection of sciatic nerve degeneration and regeneration were performed at 4 weeks after the nerve injury.The results showed:(1)At 3 days after the sciatic nerve injury,OX-42-irinthe ventral horn of spinal cord begantoincrease significantly(P<0.05);(2)The number ratio of motoneurons in ventral horn of spinal cord in ipsilateral to contralateral for injury decreased markedly(P<0.05),in-dicating the numbers of ipsilateral motoneuroanl survival decreased;(3)Histological assessment showed the poor regeneration of the in-jured nerves;(4)Simvastatin(an inhibitor of cholesterol biosynthesis,having potential immunomodulatory capacities)facilitated the mi-eroglial activation.the motoneuronal survival and sciatic nerve regeneration were better than non-simvastatin-treated vehicle rats.The pres-ent results suggest that mieroglia activation in the ventral horns ofthe spinal cord may play an important protective role in the nerve regener-ation after peripheral nerve injury of the rat.

Objective To investigate the expression and clinical significance of apoptosis inhibitory protein, Livin and Smac,in pancreatic carcinoma. Methods The expressions of Livin and Smac protein in 46 cases of pancreatic carcinoma tissues and 15 cases of insulinoma tissues and 14 cases of normal pancreatic tissues were examined by using immunohistochemical SP staining, and its relationship with clinicopathological parameters was analyzed. Results The positive expression rates of Llivin protein were 73.9％ ( 34/46),73.3％ (11/15) and 14.3％ (2/14) in pancreatic carcinoma, insulinoma and normal pancreatic tissue. Livin was highly expressed in pancreatic carcinoma and insulinoma, but there was no significant difference between the two groups, however, both were significantly higher than that in normal pancreatic tissues group ( P ＜ 0.05 ). The expression of Livin was significantly correlated with lymph node metastasis, histopathological grading and clinical staging (P ＜ 0.05 or P ＜0.01 ). The positive expression rates of Smac protein were 39.1％ (18/46), 100％ ( 15/15 ) and 92.9％ (13/14) in pancreatic carcinoma, insulinoma and normal pancreatic tissue. Smac was highly expressed in normal pancreatic tissues and insulinoma, but there was no significant difference between the two groups, however, both were significantly higher than that in pancreatic cancer group (P ＜ 0.05 ). The expression rote of Smac protein was significantly correlated with lymph node metastasis, histopathological grading, chnical staging and patients' age (P ＜0.05 or P ＜0.01 ).Conclusions Livin protein may play an important role in genesis and development of pancreatic carcinoma,but Smac protein may play a role in preventing the development of pancreatic carcinoma.

Objective To investigate the effects of levofloxacin,ciprofloxacin,ceftazidime,pip-eracillin,cefoperazone/sulbactam,erythromycin,sulfamethoxazole and gentamycin on the bacterial biofilms of Stenotrophomonas mahophilia.Methotis Biofilm and conventional susceptibilities were determined for S.maltophilia isolates from 42 patients.The model of S.maltophilia biofflms in vitro was developed in the Mueller-Hinton broth--micmtiter inoculator or silica films.After antibiotic challenge plate 20 h,each plate was sonicated and the absorbance value at 620 nm(A620)was measured on a microtiter plate colorimeter be-fore and after incubation for 6 h.Then the biofilm inhibitory concentrations were calculated.Finally,based on the acquired data.the experiments of combinafion effects of erythromycin with the 3 antibiotic agents on the formed biofilms of 5 picked strains were designed and worked out.Results The sensitive rate of 42 S.maltaphilia to levofloxacin.sulfamethoxazole and piperacillin were 83.33%,66.67%and 54.76%,re-spectively.The bilfilm inhibitory concentrations were much higher than the corresponding minimal inhibitory concentrateion after formed biofflms.Conclusion Forty-two S.maltophilia are multi-resistant to antibiotic agent.And levofioxacin may have a better effect against biofilms compared with others.The inhibition effect of combination erythromycin with levofloxacin is more obvious among all the 3 antibiotic agents.

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Objective:To establish an experimental model for intracellular antibacteria and endotoxin neutralization in vitro to detect the antibacterial and endotoxin neutralization activity of the muBPI_(25) protein.Methods: RAW264.7 cells were transfected with pcDNA3.1(+)muBPI_(36-259), and then were infected with intracellular bacterial of either G ~+/G~-to establish the experimental model of intracellalar antibacteria.The RAW264.7 cells were co-transfected with the pSecTag2B-muBPI_(36-259) and dual-luciferase reporter gene plasmids for establishment of the experimental model of endotoxin neutralization.Results:The experimental model of intracellular antibacteria confirmed that the muBPI_(25) protein could inhibit/kill Salmonella typhi.The experimental model of endotoxin neutralization indicated that the muBPI_(25) protein could neutralize endotoxin.Conelusion: We firstly demonstrate that murine BPI N-terminal functional fragment(muBPI_(25) protein)can inhibit/kill Salmonella typhi,and can neutralize, its lysating product, endotoxin.

Tetanic stimulation of the sciatic nerve (TSS) induces long-term potentiation (LTP) of both C- and A-fiber-evoked field potentials in the spinal dorsal horn and long-lasting mechanical allodynia in rats. Though central mechanisms underlying those phenomena have been well studied, peripheral mechanisms still remain poorly known. Nuclear factor kappa B (NFκB) is an important transcription factor. In the spinal cord, NFκB plays a key role in regulating the expression of numerous pro-inflammation factors and contributes to glial activation in central nervous system, suggesting the involvement of spinal NFκB in central sensitization. To address whether NFκB in the dorsal root ganglion (DRG) participates in peripheral sensitization, we examined NFκB expression in the DRG and the effect of inhibiting NFκB activation on neuropathic pain using behavior test, Western blot analysis and immunohistochemical approaches. The results showed that TSS induced long-lasting mechanical allodynia in bilateral hind paws and increased phospho-NFκB expression in the bilateral DRG. The activated NFκB mainly expressed in nuclei not only of neurons, but also of Schwann cells and satellite glial cells. Moreover, NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly alleviated TSS-induced allodynia. Our results suggest that peripheral NFκB may be involved in TSS-induced neuropathic pain, and provide new evidence for the peripheral mechanism of 'mirror pain'.
Animals ; Ganglia, Spinal ; metabolism ; Hyperalgesia ; physiopathology ; Long-Term Potentiation ; NF-kappa B ; metabolism ; Neuroglia ; metabolism ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Schwann Cells ; metabolism ; Sciatic Neuropathy ; physiopathology ; Signal Transduction ; Spinal Cord ; metabolism

OBJECTIVETo observe the effects of cryopreserved (-70 degrees C) neural stem cells (NSCs) transplantation on the axon regeneration after the spinal cord injury (SCI) of rats.

METHODSNeural stem cells were cultured from the hippocampus of the rat's embryo and identified by immunocytochemistry of nestin, then NSCs in logarithmic phage were cryopreserved (-70 degrees C) for 2 weeks. Seven days after the operation of SCI, the NSCs in were transplanted into the injured site immediately. Thirty six adult Wistar rats were randomly divided into three groups: spinal cord injury treated with transplantation of NSCs to the injured site (Group A), spinal cord injury received DMEM solution (Group B), control group (Group C). Then NSCs labeled with Brdu were detected by immunohistochemisty, and the reconstruction of spinal cord were detected by horseradish peroxidase (HRP) staining.

RESULTSNSCs can be detected in the spinal cord after transplantation. The number of HRP positive cells of Group A was higher than that of Group B.

CONCLUSIONThe transplantation of cryopreserved NSCs can survived in the injured site and promote the reconstruction. It may be a progress in the repairing of the SCI by cells transplantation.

Animals ; Axons ; physiology ; Cryopreservation ; Male ; Nerve Regeneration ; Rats ; Rats, Wistar ; Spinal Cord Injuries ; physiopathology ; therapy ; Stem Cell Transplantation

BACKGROUNDInfections caused by gram-negative bacteria (GNB) often lead to high mortality in common clinical settings. The effect of traditional antibiotic therapy is hindered by drug-resistant bacteria and unneutralizable endotoxin. Few effective methods can protect high risk patients from bacterial infection. This study explored the protection of adeno-associated virus 2 (AAV2)-bacteriacidal permeability increasing protein 700 (BPI(700))-fragment crystallizable gamma one 700 (Fc gamma1(700)) chimeric gene transferred mice against the minimal lethal dose (MLD) of E. coli and application of gene therapy for bacterial infection.

METHODSAfter AAV2-BPI(700)-Fc gamma1(700) virus transfection, dot blotting and Western blotting were used to detect the target gene products in Chinese hamster ovary-K1 cells (CHO-K1cells). Reverse transcription-polymerase chain reaction and immunohistochemical assay were carried out to show the target gene expression in mice. Modified BPI-enzyme linked immunosorbent assay was used to identify the target gene products in murine serum. The protection of BPI(700)-Fc gamma1(700) gene transferred mice was examined by survival rate after MLD E. coli challenge. Colony forming unit (CFU) count, limulus amebocyte lysate kit and cytokine kit were used to quantify the bacteria, the level of endotoxin, and proinflammatory cytokine.

RESULTSBPI(1-199)-Fc gamma1 protein was identified in the CHO-K1 cell culture supernatant, injected muscles and serum of the gene transferred mice. After MLD E. coli challenge, the survival rate of AAV2-BPI(700)-Fc gamma1(700) gene transferred mice (36.7%) was significantly higher than that of AAV2-enhanced green fluorescent protein (AAV2-EGFP) gene transferred mice (3.3%) and PBS control mice (5.6%). The survival rate of AAV2-BPI(700)-Fc gamma1(700) gene transferred mice treated with cefuroxime sodium was 65.0%. The bacterium number in main viscera, the levels of endotoxin and proinflammatory cytokine (tumor necrosis factor-alpha and interleukin-1beta) in serum of the AAV2-BPI(700)-Fc gamma1(700) gene transferred mice were markedly lower than that of PBS control mice (P < 0.01).

CONCLUSIONSAAV2-BPI(700)-Fc gamma1(700) gene transferred mice can resist MLD E. coli infection through expressing BPI(1-199)-Fc gamma1 protein. Our findings suggested that AAV2 mediated BPI(700)-Fc gamma1(700) gene delivery could be used for protection and treatment of clinical GNB infection in high-risk individuals.

Animals ; Anti-Bacterial Agents ; therapeutic use ; Antimicrobial Cationic Peptides ; Blood Proteins ; CHO Cells ; Cricetinae ; Dependovirus ; genetics ; Disease Models, Animal ; Escherichia coli Infections ; therapy ; Gene Transfer, Horizontal ; Genetic Therapy ; Mice ; Mice, Inbred BALB C ; Proteins ; genetics ; Receptors, IgG ; genetics ; Recombinant Fusion Proteins ; genetics