BACKGROUND: Myelin sheath related inhibitors have been found to have great impact on microenvironment of axon regeneration. Traditional Chinese medicine is gradual y becoming a research hotspot on improving microenvironment of nerve regeneration with its advantage on multiple factors and targets.
OBJECTIVE: To clarify the effect of Jisuikang on Nogo-66 receptor NgR expression after spinal cord injury.
METHODS: 144 rats were randomly divided into six groups: sham surgery group, model group, prednisone group, high-, moderate- and low-dose Jisuikang groups (n=24). Animal models of spinal cord injury were established by the modified Allen’s method in the later five groups. Rats in the prednisone group were daily given 0.06 g/kg prednisone acetate by lavage, once a day. Rats in the high-, moderate- and low-dose Jisuikang groups were daily intragastrically given 12.5, 25 and 50 g/kg Jisuikang, once a day. Rats in the sham surgery and model groups were intragastrically daily given 20 mL of saline, once a day. Rats in each group were administered drugs until death.
RESULTS AND CONCLUSION: Compared with the model group, NgR protein and mRNA expression levels were significantly lower in the prednisone, moderate-and low-dose Jisuikang groups. These data suggested that Jisuikang can improve the recovery of neurological function after spinal cord injury and effectively inhibit NgR protein expression at the site of injury so as to suppress the microenvironment factors harmful to nerve regeneration and further improve the microenvironment of nerve regeneration. Subject headings: Drugs, Chinese Herbal; Spinal Cord Injuries; Axons; Tissue Engineering

Objective To explore the effect of Jisuikang on neural functional recovery, and expression of brain-derived neurotrophic factor (BDNF) protein and mRNA level after spinal cord injury (SCI). Methods 144 female Sprague-Dawley rats, weighted 180 to 220 g, were used for experiment. 24 rats were randomly extracted into sham group (Group A), which had their vertebral plates and spines bitten away only.The others were randomly divided into model group (Group B), prednison group (Group C), and high, middle and low doses of Jisuikang group (Groups D to F) after SCI, 24 rats in each group. Group C was given 0.06 g/(kg ⋅ d) prednison, and Groups D to F were given 50, 25 and 12.5 g/(kg ⋅d) Jisuikang respectively, which were given 20 ml/(kg ⋅d) volume by intragastric administration. Groups A and B were given the same volume of normal saline (NS). The Basso-Beattie-Bresnahan (BBB) scores and oblique board test were applied to test the postoperative results 24 hours, 3, 7 and 14 days after SCI. The rats were executed and the spinal cord tissues were extracted 3, 7 and 14 days after SCI. Immunohistochemistry, Western blotting and RQ-PCR were applied to test the expression of protein and mRNA of BDNF. Results BBB scores and angle of oblique board test were significantly lower in Groups B to F than in Group A 24 hours after SCI (P<0.01). BBB scores were higher in both Groups C and E than in Group B 3 to 14 days after SCI (P<0.05), and was significantly higher in Group E than in the other groups 14 days after SCI (P<0.01). The results of immunohistochemistry and Western blotting showed that the protein expression of BDNF were significantly higher in Groups C and E than in Group B at different time points in the injured area after SCI (P<0.01), while there was no significant difference between Groups C and E (P>0.05). The results of RQ-PCR showed that prednisone and Jisuikang promoted the expression of BDNF mRNA. Group C (prednisone) had a most obvious effect at the beginning while Group E was better than Group C 14 days after SCI. Conclusion Jisuikang can promote the neural functional recovery and the expression of BDNF on both protein and mRNA level in SCI rats.

Objective To observe the effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on the ability of learning and memory and the expressions of JNK, Bcl-2 and Bax in hippocampus in diabetic rats with depression; To explore the protective mechanism of hippocampal damage in diabetic rats with depression. Methods High-fat gavage combined with intravenous injection of STZ was used to establish the model of diabetic rats. 28 days of chronic stress was given continuously and diabetic rats complicated with depression were built successfully. Then rats were randomly divided into 6 groups, including normal, model, positive medicine, high-, medium-, and low-dose of ZJJF groups. After the last administration, Morris water maze was used to detect escape latency time;Western blot was used to disclose the protein expressions of JNK, Bcl-2 and Bax in rat hippocampaus;RT-PCR was used to test the gene expressions of JNK and Bcl-2 and Bax. Results Compared with the normal group, escape latency time in model rats was significant longer (P<0.01), the protein and gene expression of JNK and Bax in rat hippocampaus significantly increased, Bcl-2 was markedly decreased (P<0.05, P<0.01);Compared with the model group, escape latency time in positive medicine group and high-dose of ZJJF group was significant shorter (P<0.01), the protein and gene expressions of JNK and Bax significantly decreased, and Bcl-2 markedly increased (P<0.05, P<0.01). Conclusion ZJJF can significantly improve the ability of learning and memory in diabetic rats with depression, which might be associated with preventing neuronal apoptosis in hippocampus.

Objective To clarify the effects of Jisuikang on expression levels of BDNF and NGF protein in serum of rats with spinal cord injury;To explore its probable mechanism to improve the axon regeneration microenvironment and resistance spinal cord injury.Methods Ninety SD rats were chosen to establish acute spinal cord injury model through modified Allen's method. 15 rats were chosen randomly as sham-operation group, and the other 75 rats were randomly divided into model group, prednisone group and high-, medium-, and low-doseJisuikang groups. All administration groups were given relevant medicine for gavage, while rats in sham-operation group and model group were given normal saline with the same volume for gavage. The activity and death condition of rats were recorded. Rats were put to death on the 3rd, 7th and 14th d of intervention for carotid artery blood collection. The expressions of BDNF and NGF in serum were detected by ELISA.Results After modeling, the rats in model group showed a typical paraplegia syndrome. 3 day after operation, BDNF showed no statistical significance between model group and prednisone group, while each treatment group showed significant difference when compared with prednisone group (P<0.05,P<0.01). 7 d and 14 d after operation, compared with the model group, BDNF of prednisone group and medium-dose Jisuikang group showed statistical significance, and there was no significant difference between prednisone group and medium-dose Jisuikang group (P<0.05,P<0.01). The expression of NGF in each treatment group at each time point with the prednisone group showed statistical significance. 3 d and 7 d after operation, among prednisone group, high- and medium-doseJisuikang groups, the expression of NGF was significantly higher than model group. 14 d after operation, compared with the model group, the expression of NGF in medium- and low-dose Jisuikang groups and prednisone group still maintained at a relatively high level, with statistical significance (P<0.05,P<0.01).Conclusion Jisuikang can effectively promote the expressions of BDNF and NGF in serum after spinal cord injury and maintained at a relatively high level, so as to improve the microenvironment of axonal regeneration and promote nerve regeneration.

With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

AIM: To investigate the effects of octreotide on metabolism in the A549 cells treated with lipopo-lysaccharides ( LPS).METHODS: The technologies of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) were used to test the metabolism of lung A549 cells subject to different treat-ment with LPS and/or octreotide.The results were visualized and checked by chromatogram, and the corresponding intensi-ty data were analyzed by the principal component analysis(PCA)method.The metabolites with different expression and the underlying interaction network were resolved.RESULTS: The metabolism analysis by LC/MS method indicated that there were different expression levels between different treated groups.Further analysis was carried out by orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and the different expressed metabolites were obtained, which were mainly amino acids and phospholipids.By analyzing with GC/MS method and t-test, the different expressed metabolites were mainly organic acid, saccharides and amino acid metabolite.The interaction network diagram was constructed about the response of A549 cells induced by LPS and/or octreotide, including glycolysis/gluconenogenesis, tryptophan metabo-lism, galactose metabolism, urine cycle and citrate cycle.Fourteen key components were found such as serotonin, indole, threonine, serine, glucose, phenylalanine, lactose, fumarate, 4-hydroxyphenyllactate, aspartate, asparagine, putrescine, proline and succinate.CONCLUSION: In octreotide treated LPS-induced A549 cells, the main metabolites are organic acid, saccharides, amino acids and phospholipids.The interaction network is constructed, including 5 metabolic pathways
and 14 key components.

Objective To investigate the regulating effects of Zuogui Jiangtang Jieyu Formula (ZJJF) on Bcl-2, Bax and Caspase-8 in hippocampus neuron damage in diabetes mellitus with depression (DD). Methods Hippocampal neurons from 18 d pregnant rats were primitively cultivated, and then combination of glucose and corticosterone was used to construct DD simulation environment. Cultivated hippocampal neurons were randomly divided into normal group, blank serum group, model group, positive medicine (metformin+fluoxetine) serum group and to-be-tested medicine (ZJJF) serum group. Normal group and model group were given same amount culture medium, while other group were given relevant amont of 10％ medicine serum or blank serum. After modeling intervention for 18 h,Hoechst staining was used to detect the apoptosis of hippocampal neurons. The expression of Bcl-2, Bax and Caspase-8 was detected by high content analysis. Results Compared with the control group, hippocampal neuron dendrites ruptured or decreased, neural network connection decreased, cells showed significant staining, broken, uneven distribution of light spots, the expression of Bcl-2 protein decreased significantly (P<0.05), but Bax and Caspase-8 were increased (P<0.05, P<0.01). Compared with the model group, hippocampal neurons in both positive medicine serum group and ZJJF serum group gradually recovered. Hoechst staining showed that the nuclei were significantly homogenized, local highlights were significantly reduced, Bcl-2 protein expression levels were significantly increased (P<0.05, P<0.01), while Bax and Caspase-8 were obviously down-regulated (P<0.05, P<0.01). Conclusion ZJJF has protective effects on hippocampal neurons in DD of model rats, and its mechanism is related to regulating the expression of Bcl-2, Bax and Caspase-8 in hippocampus neuron.

AIM: To observe the effect of Chinese medicine compound JiSuiKang on the microglia infiltration and neuron survival at the spinal cord injury area of rats. METHODS: Sixty SD rats were randomly divided into sham operation group (Sham), model group (Ctrl), JSK low (JSK-L), JSK medium (JSK-M) and JSK high (JSK-H) dose group, prednisone group. The model of rat spinal cord injury (SCI) was established by improved Allen's method. After the operation, each group was intervened in different ways, and then we assessed the double hind limb motor function score in rats (BBB score). The heart perfusion was done and the spinal cord tissues from the injury area were taken. ELISA tests were used to detect the expression of inflammatory factors. The spinal cord tissue was sliced into sections and then immunofluorescence stained of CD11b/c and beta 3-Tubulin to observe the infiltration of microglia and the growth of neurons under the inverted fluorescence microscope. RESULTS:The BBB score of Sham, JSK-L, JSK-M, JSK-H and prednisone group were higher than Ctrl(P<0.05). For the expression of inflammation, the expressions of IL-1 in group Sham, JSK-L, JSK-M, JSK-H and prednisone were lower than that of Ctrl (P<0.05). For the percentage of microglia infiltration, JSK-L, JSK-M, JSK-H and prednisone were all lower than that of Ctrl (P<0.05), and there was no significant difference between JSK-H and prednisone(P>0.05). For the growth state of the neuron, the JSK-L, JSK-M, JSK-H, prednisone group were better than Ctrl (P<0.01), and JSK-H was better than JSK-L and JSK-M (P<0.05). CONCLUSION: The Chinese medicine compound JSK inhibits the migration and invasion of microglia in SCI, promotes the recovery of damaged neurons and motor function in SCI rats.

Objective To propose a new suggestion for the clinical downstaging of nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT) without changing the current T,N,and M staging system.Methods We reviewed the records of 536 NPC patients treated in Sun Yat-Sen University Cancer Center from January 2002 to December 2006.The Kaplan-Meier method was used to calculate the disease-specific survival (DSS) rate,and the log-rank test was used for survival difference analysis.The Cox regression model was used to calculate the hazard ratio (HR) of each subset.ResultsAccording to the 7th edition of UICC/AJCC staging system,the 5-year DSS rates of stage Ⅰ-Ⅲ patients (except T3N2M0) were all more than 85%(P>0.05),those of stage ⅣA and ⅣB patients were 71.8% and 46.2%,respectively (P=0.171),and that of stage ⅠVC patients was only 24.0%.In stage Ⅲ,the 5-year DSS rate of non-T3N2M0 patients (91.5%) was significantly higher than that of T3N2M0 patients (78.6%)(P=0.042),but there was no significant difference in DSS between T3N2M0 patients and stage ⅣA and ⅣB patients.Based on the above results,new stage Ⅰ included T1-3N0-1M0 and T1-2N2M0,new stage Ⅱ included T3N2M0,T4N0-2M0,and TxN3M0,and new stage Ⅲ included TxNxM1.The 5-year DSS rates of new stage Ⅰ,Ⅱ,and Ⅲ patients were 93.3%,72.7%,and 24.0%,respectively (P=0.000).Compared with new stage Ⅰ patients,new stage Ⅱ and Ⅲ patients had HRs of 4.01 and 16.76,respectively,for 5-year DSS.Conclusions In the era of IMRT,the new clinical staging system (stages Ⅰ,Ⅱ,and Ⅲ) helps with prognostic evaluation and clinical treatment.

Neurogenic bowel dysfunction (NBD) manifested as constipation and fecal incontinence often occurs after spinal cord injury (SCI).NBD affects patients' quality of life and is an urgent clinical problem to be solved.The mechanism of NBD is related to central and autonomic nervous system dysfunction,intestinal nervous system dysfunction,changes in intestinal microorganism composition and abnormal content of neurotransmitters.The evaluation method of NBD is mainly based on scoring and imaging,which lacks unified criteria,and the treatment method for NBD is the combination of traditional Chinese and Western medicine.The author summarizes the mechanism,evaluation method,treatment and nursing of NBD in order to provide new insight into these aspects to improve clinical efficacy.