AIM: To evaluate colon-oriented delivery characteristics of berberine hydrochloricde(BH) containing carboxymethyl konjac glucomannan(CMKGM) pellets. METHODS: BH-containing CMKGM pellets(pellets group) and BH-containing carboxymethyl cellulose suspension(control group) were intragastric administrated to rats at the dose of 50 mg/kg,respectively.Blood samples were obtained from the rat femoral artery,the gastric、entric、cecal、colonic tissues and their contents sampled at a given interval to measure the concentration of BH by HPLC.The bar charts of relative content of BH in different parts of the gastrointestinal tract and theirs contents were drawn.Drug delivery index(DDI) was calculated. RESULTS: Compared with the control group,the concentration and distribution of BH in gastric、enteric tissue and their contents decreased significantly,but in cecal、colonic tissue and their contents less at first,and more than the control group after 2～6 h.The DDI values of the pellets to gastric,enteric,cecal,colonic tissue and their contents were 0.392 4,0.478 6,3.916,4.193,(0.162 8,)0.619 4,3.843,4.087 against the control group,respectively. CONCLUSION: CMKGM pellets may be a useful colon-specific drug delivery system for BH.

Recent studies in the realm of metabolic chemistry of traditional Chinese drugs (TCD),appeared in literature were reviewed. Methods for such study were enumerated and commented upon.Some problems that arised in the study were discussed. It was suggested that the study of metabolic chem-istry on TCD and its compounded preparations should be further pursued.

Objective To investigate the prevalence of depression in maintenance hemodialysis (MHD) patients. Additionally,to explore the relationship between depression and microinflammation,serum zinc levels and malnutrition in MHI) patients.Methods One hundred fifty-seven MHD patients were enrolled in this study.The patients were divided into two groups:depressed patients and non-depressed patients,according to the Beck Depression Inventory.The following data were collected:social factors,biochemical index,serum zinc levels,malnutrition-inflammation (MIS) score and IPI score.Binary logistic regression analysis was performed.Results Symptoms of depression were exhibited by 45.2％ of MHD patients (71/157 ).Symptoms of moderate or severe depression were exhibited by 24.2 ％ of the patients ( 38/157 ).However,signicant differences were shown in age [( 62 ± 11 ) vs.( 50 ± 13 ) years old],MIS score [( 7.2 ± 2.2 ) vs.( 3.3 ± 1.6 ) scores],white blood cell count [( 6.4 ± 1.8 ) × 109/L vs.( 5.8 ±1.5) × 109/L],high sensitivity C-reactive protein (hsCRP) [(9 ±6) vs.(4 ±4) mg/L],hemoglobin [(10.7±1.5) vs.(11.3±1.5) g/L],albumin[(33±4) vs.(37 ±3) g/L],fasting glucose [(6.7±3.5) vs.(5.6±2.1) mmol/L],serum zinc [(8.5±2.6) vs.(10.1 ±2.9) μmol/L] between depressed patients and non-depressed patients ( All P ＜ 0.05 ). Binary logistic regressive analysis revealed that the independent risk factors of depression in MHD patients were their MIS score ( OR =2.908,95％ CI =2.037 -4.151 ),as well as their hsCRP( OR =1.217,95％ CI=1.075 - 1.370),serum zinc and fasting glucose levels(OR=1.315,95％CI=1.039 - 1.664).Conclusions There was a high prevalence of depression in MHD patients.Depression is also highly correlated with microinflammation,serum zinc levels,and malnutrition.MIS scores,hsCRP,serum zinc levels and fasting glucose levels.

Objective To establish the electric controlled cortical impact (eCCI)-induced traumatic brain injury (TBI) model in rats with different severity in degree,which may serve as a suitable platform to provide experimental evidence for the pathophysiological following TBI.Methods A total of 40 male Wistar rats were randomly divided into 3 experimental groups and sham group.TBI rats (n=10/group) were positioned beneath the controlled cortical impactor device (eCCI) and subjected to impact injury at 2 mm depth of penetration,for a sustained depression of 200 ms,at 4 m/s,5 m/s,6 m/s velocity for mild,moderate,and severe TBI,respectively.Sham-operated rats (n=10) underwent identical surgical procedures,including craniotomy,without receiving the cortical impact.Neurological function and regional cerebral flow (24 h after CCI),contusion volume,histopathological,and ultrastructural changes (48 h after CCI) were measured,respectively.Results The severity of the pathological changes in rats was increased as the injury aggravated.The eCCI device impacted the brain at 4 m/s,5 m/s,6 m/s velocity for mild,moderate,and severe TBI,respectively.TBI groups showed impaired neurological function,and decreased rCBF lower than that of sham-operated group (all P＜0.01).Furthermore,neuronal pathological abnormalities in TBI groups,including neuron shrinking,perineuronal vacuole,and structural abnormalities of mitochondria.Increased severity of injury was apparent following the increased level of the impacted velocity,and significant differences were observed between TBI groups (P＜0.05).Conclusion The TBI animal model with mild,moderate,and severe brain injury can be established successfully by 4 m/s,5 m/s,and 6 m/s of impact velocity respectively with the eCCI-6.3 device.The novel eCCI-induced TBI model in rats possibly serves as a novel useful approach in the development of TBI models.

Objective To explore aspirin resistance (AR) and its relevant influencing factors in patients on maintenance hemodialysis (MHD).Methods Patients on MHD who visited Beijing Chaoyang Hospital from June 1 to 30,2011 were enrolled in this study.A total of 150 age and gender matched individuals with normal renal function were taken as control group.Anthropometric data,biochemistry parameters,ultrasonography and thromboelastograph (TEG) were inspected in the both groups.AR was defined as inhibiting rate of acetylsalicylic acid drugs [MA (AA)] ＞ 50％ by TEG.Results Among the total 391 patients on MHD,hypercoagulation was found in 18 patients (4.6％),nomal coagulation in 288 patients (73.7％) and hypocoagulation in 85 patients (21.7％).Pearson's correlation analysis revealed that the reaction time (R) and the thrombus maxithrombelastic degree (MA) values were not correlated with the levels of hemoglobin and platelet in MHD patients.A total of 306 patients with hypercoagulation and normal coagulation were chosen as the MHD group.Compared with the control group,higher high sensitivity C reactive protein (hsCRP),homocysteine (Hcy) and R value were observed in the MHD group (P ＜ 0.05),while MA was significantly lower in the MHD group.Statistically higher incidence of AR was shown in the MHD group (48.0％ vs 20.0％,P =0.00).Patients in the MHD group were divided into the AR group and the aspirin sensitive (AS) group by the result of TEG.Compared with the AS group,patients in the AR group were found to be older with a higher female/male ratio,longer dialysis sustained time,higher ratio of diabetes history,higher hsCRP,Hcy and fasting blood glucose (FBG) and MA.They also manifested a higher incidence of cardiovascular and cerebrovascular diseases,peripheral vascular disease and arteriovenous fistulas with thrombosis with more spots of carotid artery and higher intima thickness of carotid artery (IMT) (all P values ＜0.05).Lower R value was shown in the AR group.Binary logistic regressive analysis revealed that the ratio of diabetes history,age and dialysis sustained time.Hcy and hsCRP were the independent risk factors for AR in patients on MHD.A total of 289 patients on MHD with atherosclerosis were followed up for the mean time of 18.0 months with no hemorrhage found in the process.Cox proportional hazards regression modeling demonstrated that AR was associated with the major adverse longterm outcome of the vascular events [HR =0.40,95 ％ CI 0.29-0.72,P =0.00].Conclusions The ratio of platetet activation in patients on MHD is significantly lower than in those with normal renal function.Small dose of aspirin could be prescribed for the patients on MHD with atherosclerosis to prevent vascular events.The incidence of AR is 48.0％ in the MHD group and the independent risk factors for AR in MHD patients are the ratio of diabetes history,age,dialysis sustained time,Hcy and hsCRP.AR is associated with the major adverse long-term outcome of acute vascular events.

ObjectiveTo investigate the roles of 11 β-hydroxysteroid dehydrogenase type 1 ( 11 β-HSD1 )on hippocampus of rat with chronic unpredictable mild stress (CUMS).MethodsTwenty-four male SpragueDawley rats were randomly divided into control group and depressive model group. Chronic unpredictable mild stress (CUMS) was used to make up depressive animal model.Behavioral changes were recorded by body weight measuring,sucrose consumption test (SCT) and open field test (OFT),respectively.The mRNA transcription of 11β-HSD1 in hippocampus tissues of the rats were detected by real-time RT-PCR,and the protein expression of 11β-HSD1 were detected by western blot and immunofluorescence.ResultsBcforc starting CUMS protocol,the rats exhibited equivalent weight and sucrose consumption.Twenty-eight days after CUMS protocol,behavior parameters such as body weight,sucrose consumption,nunber of crossing,and number of rearing were significantly decreased in rats exposed to CUMS group compared with control group (P ＜ 0.05,P ＜ 0.01 ).Correspondingly,realtime RT-PCR assays showed the mRNA expression of 11 β-HSD1 in the hippocampus of CUMS group,which was (31 ±9) ％ lower than that of control group.Meanwhile,the protein expression of it in CUMS group was lower than that of control group (P ＜ 0.05 ).Inmunofluorescence revealed that the number of positive 11 3-HSD1 cells was high (223 ± 13) in the control group,while the number was decreased prominently (92 ± 11 ) in the CUMS group (P ＜ 0.01 ).ConclusionDepressive behavior of rats is induced and the expression of 11 β-HSD1 in the hippocampus is decreased prominently by CUMS,the mechanism of which is at least related to the low expression of 11β-HSD1 and disturbance of glucocorticoid metabolism caused by CUMS.

Objective To study the effect of brain-derived neurotrophic factor (BDNF) on the environmental nutrition and neural differentiation of the transplanted stem cells under hypothermia.Methods The BDNF gene mediated by liposome was transfected into 293T cell line, and ELISA assay was applied to find the peak time of BDNF expression. When BDNF was highly expressed, the supernatant was collected for establishment of SD rat models of brain injury. The rats were divided into Group A (stem cell transplantation group) and Group B (stem cell transplantation and BDNF group). Rats in both groups were under hypothermia treatment for five days. Four and eight days later ( three days from rewarming), rat brain tissues were obtained to detect the expressions of proliferating cell nuclear antigen (PCNA), nestin, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) by immunohistochemical method and to detect the apoptosis by in situ hybridization. Finally, the nerve function scores were obtained for evaluation of the nerve function. Results The ELISA showed that the high level of BDNF expression was at 48 to 60 hours after gene transfection. PCNA and nestin were highly expressed, while NES and GFAP showed nil or low level of expression in both groups at the fourth day after hypothermia, with little apoptotic cells especially in the Group B (P ＜0.05). The expressions of PCNA and nestin were decreased, but the expressions of NSE and GFAP were increased at the third day after rewarming. The positive rate of NSE expression in the Group B was much higher and the apoptotic cells were much less compared with the Group A ( P ＜ 0. 05 ). A better nerve score was obtained in the Group B. Conclusion BDNF can enhance the survival rate of the transplanted stem cells and induce their differentiation into neurons under hypothermia.

Platelet play an important role in cerebral ischemial nerve injury. Aspirin (ASA) had been used to treat and prevent stroke in clinic. 30 rabbits were randomly divided into A, B and C groups. In group A ASA was given orally at a daily dosage of 15 mg/kg per rabbit for 5 days before cerebral ischemia; group B cerebral ischemia without giving ASA, and group C was normal rabbits as controls. The cerebral ischemial model was produced by occluding bilateral carotid arteries and bleeding from femoral artery. The results indicated that there was an obvious decrease of PAgT and TXA_2 and had no significance changes in free radicals increasing and Ca~(2+) rising from cerebral tissue in group A. The cerebral edema of group A was less severe than group B. It seemed that ASA had a protective effect on the nerve injury of cerebral ischemia. The derangement of ASA, platelet, free radicals and calcium ions interrelation and their significance on the nerve injury should be further studied.

Objective To investigate prevalence of metabolic syndrome (MS) and its related factors in patients with maintaining hemodialysis (MHD). Methods A total of 162 cases on MHD in Beijing Chaoyang Hospital during June to December 2010, were enrolled in this study and divided into MS group and non-MS group according to the diagnostic criteria for MS set by the International Diabetes Federation. Anthropometric and blood biochemical characteristics of the two groups were compared with t-test and x2 test Risk factors for MS were explored with binary logistic regression analysis. Results Prevalence of MS was 40. 7% (66/162) . There was significant difference found in body mass index [(24. 2 ±3. 1) vs. (21. 6 ±2. 7) kg/m2], waistline circumference[(93 ±8) vs. (79 ±7)cm] , white blood cell count [(6. 8 ± 1. 5) × 109/L vs. (5. 6 ± 1. 4) × 109/L] , hypersensitive serum C-reactive protein [(7 ± 5)vs. (4 ±3) mg/L], high-density lipoprotein-cholesterol [(0. 99 ±0. 26)vs. (1.39 ±0.39) mmol/L], low-density lipoprotein-cholesterol [(2. 5 ± 0. 8) vs. ( 2. 1 ± 0. 7) mmol/L], triglyceride ( TG) [( 2. 1 ±1.1 )vs. (1.3±0.8) mmol/L], fasting blood glucose [(5.9±2. 7)vs. (4.8±1.3) mmol/L], serum level of iron [(16±7)vs. (13 ±5) μmol/L], uric acid [(429±114) vs. (388±88) (μmol/L], and carbon dioxide combining power (CO2CP) [(22 ±4)vs. (23 ±4) mmol/L]between MS group and non-MS group (All P < 0.05 ) . But there was no significant difference found in subjective global assessment of nutritional status (SGA) , thickness of skin fold of the triceps muscle (TSF) between the two groups (Both P > 0.05). Binary logistic regressive analysis revealed that serum level of iron (OR = 1.058,95% CI = 1.001 -1. 119), white blood cell count ( OR = 1. 786,95% CI = 1. 346 - 2.371) and hypersensitive serum C-reactive protein (OR = 1. 101,95% CI = 1.010 - 1.201 ) were independent risk factors for MS in MHD patients. Conclusions Morbidity of MS is high in patients with MHD, involved with inflammation process. Serum level of iron, white blood cell count and hypersensitive serum C-reactive protein are independent risk factors for MS in patients with MHD and no inevitable connection between MS and nutritional status in them is found.

Objective To observe functional changes of renal tubular epithelial cells stimulated by high mobility group protein box 1 (HMGB1) and associated mechanism.Methods Renal tubular epithelial cells (NRK52E) were divided into control group,HMGB1 group and HMGB1+ lipopolysaccharide from Rhodobactersphaeroides (LPS RS) group.Toll-like receptor 4 (TLR4) expression was detected by immunofluorescence and Western blotting.Apoptosis rate and cell cycle arrest were identified with flow cytometry.The activation of MAPK signaling pathway and NF-κB were detected by Western blotting.The IL-1,IL-6 and tissue inhibitor of metalloproteinases 2 (TIMP2) mRNA levels were measured by real-time PCR.The secretion levels of IL-1,IL-6 and TIMP2 were measured by protein chips assay.Results TLR4 was expressed by NRK52E cells.Compared with the control group,there were increased cell cycle G1 arrest,MAPK signaling pathway and NF-κB activation in HMGB1 group.Furthermore,IL-1,IL-6 and TIMP2 mRNA levels were increased and IL-1,IL-6 and TIMP2 were secreted by NRK52E when stimulated with HMGB1 (all P ＜0.05).However,effects mediated by HMGB1 stimulation could be inhibited by LPS RS (all P＜0.05).Conclusions Inflammatory activation of NRK52E cells can be mediated by the interaction of HMGB1 and TLR4.