Objective To investigate the relationship between T?cell death?associated gene 8 ( TD?AG8) and endogenous neuron?protective mechanism against oxygen?glucose deprivation and restoration ( OGD∕R)?induced apoptosis in rat neurons. Methods The primary cortical neurons obtained from fetal rats were seeded in 6?well plates at a density of 1×105 cells∕ml and divided into 5 groups using a random number table: control group ( group C, n=24 ) , group OGD∕R ( n=48 ) , TDAG8 agonist BTB09089 group (group BTB, n=24), TDAG8?siRNA group ( group siRNA, n=24), and blank vehicle group ( group V, n=24) . The medium was replaced with glucose?and serum?free Locke′s buffer, and the neu?rons were exposed to 95% N2?5% CO2 in an air?tight incubator at 37℃ for 60 min followed by routine cul?ture to establish the model of OGD∕R. In BTB, siRNA and V groups, 20 μmol∕L TDAG8 agonist
BTB09089, 200 pmol∕L TDAG8?siRNA, and 6 μl∕200 μl transfection reagent were added, respectively, at 24 h before oxygen?glucose restoration. At 6 h of oxygen?glucose restoration, the neuronal viability and a?mount of lactic dehydrogenase ( LDH) released were measured, and the expression of TDAG8 and caspase?3 mRNA in neurons was detected by fluorescent quantitative real?time polymerase chain reaction. In group OGD∕R, the expression of TDAG8 and caspase?3 was measured by Western blot at 0, 3, 6, 12 and 24 h of oxygen?glucose restoration. In C, OGD∕R, BTB, siRNA and V groups, the expression of TDAG8, caspase?3 and p?Akt was detected at 6 h of oxygen?glucose restoration. Results In group OGD∕R, the ex?pression of TDAG8 was gradually up?regulated after oxygen?glucose restoration, and the expression of caspase?3 peaked at 6 h of oxygen?glucose restoration. Compared with group C, the neuronal viability was significantly decreased, the amount of LDH released was significantly increased, and the expression of TD?AG8 and caspase?3 protein and mRNA and p?Akt was significantly up?regulated in OGD∕R, V and siRNA groups ( P<0?05) . Compared with group OGD∕R, the expression of TDAG8 protein and mRNA and p?Akt was significantly up?regulated, the expression of caspase?3 protein and mRNA was significantly down?regu?lated, the neuronal viability was significantly increased, and the amount of LDH released was significantly decreased in group BTB, the expression of TDAG8 protein and mRNA and p?Akt was significantly down?regulated, the expression of caspase?3 protein and mRNA was significantly up?regulated, the neuronal via?bility was significantly decreased, and the amount of LDH released was significantly increased in group siR?NA ( P<0?05) , and no significant change was found in the parameters mentioned above in group V ( P>0?05) . Conclusion TDAG8 is partially involved in the endogenous neuron?protective mechanism against OGD∕R?induced apoptosis in rat neurons, which may be related to activation of Akt signaling pathway.

Objective To study the protective mechanism of adenosine on intestinal barrier function in acute hemorragic necrotizing pancreatitis (AHNP) pigs; Methods Twelve small pigs were equally devided into two groups randomly after the AHNP model sitted up: (1) AHNP controll group (group A) and adenosine treated group (group B). The intestinal blood flow, intestinal permeability, bacterial culture and endotoxin in portal blood were compared between the two groups in pre and post AHNP. Results (1)The intestinal blood flow was dramatically decreased in group A, and much higher in group B than that in group A at the 8 h, 24 hour and day 7 after ANHP model was setted up (P0.001,P

Objective To assess the value of integrated 18 F-fluorodeoxyglucose (FDG) PET/CT in differentiation of malignant and benign pericardial effusion. Methods 18F-FDG PET/CT were performed in 23 patients with pericardial effusion. The detected soft tissue tumor or nodulous lession in pericardium or the thickened pericardium, with the maximum standardized uptake value( SUVmax ) ≥2.5, was defined as PET/CT-positive. The invaded lession in pericardium with SUVmax ≥2.5 was also as the positive. The difference of SUVmax of benign and malignant lesions was analyzed with two-independent-sample test of nonparametric tests. The final diagnosis was confirmed by biopsy or post-operative pathology. Results The diagnosis were confirmed with 14 malignant and 9 benign lesions. The median of SUVmax was 6.0 in malignancy group and 2.2 in benign group (z= -3. 279, P =0.001 ). According to the pathology results, there were one false negative case and two false positive cases with PET/CT imaging interpretation. The sensitivity, specificity,accuracy, positive predictive value ( PPV ) and negative predictive value ( NPV ) of 18 F-FDG PET/CT in diagnosis of benignity or malignance of pericardium effusion were 92.9% ( 13/14), 7/9, 87.0% (20/23),86.7% (13/15) and 7/8, respectively. Conclusion For the patients with pericardium effusion 18F-FDG PET/CT may be a helpful modality for malignancy differentiation

We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in that it enhances the pharmaceutical manufactures the ability to control enterprise risk and eliminate the negative impact on traditional Chinese medicine. With the widely used and ADR report concentrated Radix Bupleuri injection as an example, the author provide a new approach to post-marketing clinical research.
Bupleurum ; chemistry ; Drug Compounding ; Drug-Related Side Effects and Adverse Reactions ; etiology ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Product Surveillance, Postmarketing ; methods ; Safety

OBJECTIVETo construct an off-line hybrid bioartificial liver supporting system with human liver cell line, and study it's effect on the plasma from patients with liver failure.

METHODSWe established the bioreactor using Psu-2s (Fresenius) cultured with Hep G2 cell transfected with human augmenter of liver regeneration (hALR) gene, then constructed a hybrid bioartificial liver supporting system, at last using the bioartificial liver support system to purify the plasma treated 2 hours with serum bilirubin absorbent, separated from acute on chronic liver failure patients infected by hepatitis B virus.

RESULTSBioreactor was successful constructed. The cell viability in perigastrum of bioreactor is 85.2% and cell propagated rapidly. Before and after treating with bilirubin absorbent, serum total bilirubin was (176.19 +/- 54.14) micromol/L and (50.1 +/- 16.85) micromol/L respectively (P = 0.0002). While there were no significance difference in the level of albumin, urea and glucose. At the begin and end of treatment with bioartificial liver, serum total bilirubin was (50.10 +/- 16.85) micromol/L and (30.27 +/- 15.02) micromol/L respectively (P = 0.000), the urea and albumin increased, urea has significantly difference, but the change of albumin hasn't.

CONCLUSIONThe off-line hybrid bioartificial liver supporting system with human liver cell line were builded successfully and have synthesis and metabolism functions for acute on chronic liver failure patients.

Adult ; Artifacts ; Bilirubin ; metabolism ; Bioreactors ; standards ; Chimera ; End Stage Liver Disease ; physiopathology ; Hepatocytes ; metabolism ; physiology ; Humans ; Liver ; physiology ; Liver Failure ; Liver, Artificial ; utilization ; Male ; Middle Aged

OBJECTIVEThis study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children.

METHODSThirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N-acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls.

RESULTSMRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups.

CONCLUSIONS'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy.

Aspartic Acid ; analogs & derivatives ; analysis ; Child ; Child, Preschool ; Choline ; analysis ; Epilepsy ; diagnosis ; metabolism ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; methods ; Male ; Phosphocreatine ; analysis ; Protons

Objective To investigate whether the left ventricular delayed contraction site determined by tissue Doppler imaging might be an optimal left ventricular lead position for improved outcomes of cardiac resynchronization therapy (CRT) in patients with non-ischemic cardiomyopathy. Methods Thirty-three patients subjected to CRT were selected, and all were performed conventional ultrasound cardiography and tissue Doppler examinations before operation. The left ventricular delayed contraction site was determined according to the interval between the onset of QRS and the peak systolic velocity. Retrograde coronary venography was performed during operation, and the left ventricular lead site was selected according to the left ventricular delayed contraction site determined by tissue Doppler examination before operation. The coronary sinus lead site was determined under the guidance of X ray of dorsaventral, lateral, right anterior oblique and left anterior oblique positions. Patients were divided into group A(n=20, the left ventricular lead site was in line with the delayed contraction site) and group B (n=13, the left ventricular lead site was not in line with the delayed contraction site). Results There was no significant difference in age, NYHA grading, left ventricular end-systolic volume(LVESV), left ventricular ejection fraction(LVEF), pulmonary arterial systolic pressure, QRS width and Ts-SD between the two groups before operation(P> 0.05). Six months after CRT, there was no significant difference in NYHA grading, LVESV and mitral regurgitation(MR) grading between the two groups(P>0.05), while the increase in LVEF and decrease in LVESV of group A were more significant than those of group B (P<0.01). Conclusion In patients with non-ischemic cardiomyopathy, CRT significantly improves left ventricular performance, and the more favourable outcomes are achieved in those pace at the delayed contraction site. Tissue Doppler imaging may help to guide the implant of left ventricular lead.

Objective To evaluate Mycobacterium tuberculosis (M. tuberculosis)-specific cellular immunity in individuals with latent or active tuberculosis and human immunodeficiency virus (HIV) coinfection. Methods One hundred HIV-infected individuals in Yunnan Province were enrolled. The enzyme-linked immunospot (ELISPOT) assay using early secreted antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 was employed to detect M. tuberculosis-specific T cells in the peripheral blood. The absolute number of CD3+ CD4+and CD3+ CD8+ T cells in the peripheral blood from the enrolled subjects were determined by flow cytometry. Data were analyzed using nonparametric Mann-Whitney test. Results The prevalence of latent tuberculosis co-infection in HIV-infected individuals without any clinical evidence of active tuberculosis was 67.6%. The absolute numbers of CD3+ CD4+ (532 × 106/L) and CD3+ CD8+ (473 × 106×/L) T cell in HIV-infected individuals with latent tuberculosis co-infection were similar to those of only HIV-infeeted individuals (406 ×106×/L and 504 × 106/L). While those in HIV-infected individuals with active tuberculosis co-infection were 189 × 106/L and 293 × 106/L, respectively, which were both significantly lower than those in other two groups (U=168. 0,U=163. 0,U= 374. 0,U=147. 0, all P<0. 01). Furthermore, ESAT-6 (31/106 cells) and CFP-10 (82/106 cells) specific spot-forming cells in HIV-infected individuals with active tuberculosis co-infection were significantly less than those in HIV-infected individuals with latent tuberculosis co-infection (92 × 106 cells and 109 × 106 cells, U= 507. 0,U= 529. 5, both P<0. 01). Conclusions The prevalence of latent tuberculosis in HIV-positive individuals without any clinical evidence of active tuberculosis is high in China. Both overall cellular immunity and M. tuberculosis-specific immune response in HIV-positive individuals with active tuberculosis co-infection are severely impaired.

OBJECTIVETo investigate the association between the morphological features of biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa and the postoperative pathology.

METHODSFifty-one patients with biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa were retrospectively analyzed. Thirty-three patients underwent surgery. The morphology of lesions under endoscopy and histopathological findings of the surgical specimens were investigated.

RESULTSOf the 51 patients, 43 had superficial lesions similar to early gastric cancer under endoscopy, 8 were similar to advanced carcinoma. In the 33 surgical cases, high grade intraepithelial neoplasia of gastric mucosa was confirmed on postoperative pathological examination in 13 (39.4%) patients, adenocarcinoma was identified in the remaining 20 patients (60.6%), including 14 early gastric cancers and 6 advanced carcinomas. Thirteen cases with high grade intraepithelial neoplasia confirmed postoperatively were superficial elevated or flat lesions less than 20 mm.

CONCLUSIONSPatients with biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa have a high risk of cancer. Thus aggressive follow-up and appropriate surgical interventions are recommended to avoid misdiagnosis.

Adult ; Aged ; Aged, 80 and over ; Biopsy ; Female ; Gastric Mucosa ; pathology ; Gastroscopy ; Humans ; Male ; Middle Aged ; Prostatic Intraepithelial Neoplasia ; pathology ; Stomach Neoplasms ; pathology

Objective To evaluate the efficacy and safety in treatment of patients with mild to moderate Alzheimer’s disease (AD). Methods A total of 233 patients with mild to moderate potential AD were enrolled in a 16-week multi-center double blind clinical trial. All patients were randomized into two groups. 110 patients in galantamine group and 108 patients in donepezil group were enrolled in efficacy analysis. The scales of Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL) and The Neuropsychiatric Inventory (NPI) were used to assess the effect at both baseline and the end of 16 weeks. Safety issues, including vital signs, lab assays and ECG examinations were measured. Results Patients in both groups were obviously improved in the total score of ADAS-cog (-5.4?6.4) in the galantamine group and (-4.0?7.3) in the donepezil group, P=0.098). 76% patients of the galantamine group had a score of ADAS-cog less than 20 at the end of 16 weeks treatment, which was higher than that of the donepezil group (58%, P=0.015). The sub-score of speech ability in ADAS-cog were improved in the galantamine group (baseline 2.8?2.9,16 weeks 1.8?2.5) compared with the donepezil group (baseline 2.8?3.0, 16 weeks 2.3?2.9, P=0.035). No significant difference of ADSC-ADL and NPI scale was found between the two groups (P=0.447 and 0.936 respectively). The sleep/night behavior was improved in the donepezil group (baseline 14%, 16 weeks 10%) compared with the galantamine group (baseline 23%, 16 weeks 22%, P=0.012). Two drug-related severe adverse events occurred during the trial, which were platelet reduction in the galantamine group and acute drug-induced hepatic injury in the donepezil group. The incidence of adverse events was 44% in the galantamine group and 47% in the donepezil group respectively. Galantamine had little influence on vital signs and lab assays. Conclusion Safe and well tolerated, galantamine improves the cognition, activities of daily living and neuropsychiatric symptoms of patients with mild to moderate AD.