Biliary tract carcinoma (BTC) is a common malignancy in human digestive system.The lethality of BTC is essentially attributed to the asymptomatic growth of BTC and the lack of effective diagnostic options.The disease is therefore usually detected at an advanced stage and lost the opportunity of surgical therapy.Conventional chemotherapy and radiation therapy have been notably ineffective against BTC.There is now a real and urgent need to focus on developing novel and potent therapeutic strategies against BTC.Human epidermal growth factor receptor 2/neu (HER2/neu) is a member of the ErbB receptor tyrosine kinase family.HER2/neu is associated with tumor proliferation,invasion,and metastasis that would impact in a significant way on clinical outcome.HER/neu may become a new therapy target of BTC.

Objective To study the serum levels of melatonin,tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in multiple sclerosis (MS) patients and the correlation with disability.Methods Forty patients with multiple sclerosis were collected as MS group and 30 healthy participants were collected as control group.Serum levels of melatonin and cytokines,including IFN-γ and TNF-,were detected in all participants by the enzyme-linked immunosorbent assay (ELISA) method;disability status of patients with MS was evaluated by EDSS scale.The relevant analysis between serum melatonin,TNF-α,IFN-γ levels and EDSS score in patients with MS was conducted.Results The concentration of serum melatonin in MS group was significantly lower than control group (P＜0.01).TNF-α levels were higher than control group (P＜0.05) and the difference was statistically significant between MS patients and control group.Among MS group and control group,no significant correlation with the serum levels of IFN-γ was seen.The serum melatonin level was inversely correlated with EDSS score in MS patients (r =-0.76,P＜0.01),and positively correlated with TNF-α (r =0.83,P＜0.01) and as compared to IFN-γ,no significant correlation was found (r =0.17,P＞0.05).Conclusion The decrease of melatonin and increase of TNF-α can be a factor in the inflammatory reaction in patients with MS,and is closely related with dysfunction occurring in multiple sclerosis.Serum melatonin and TNF-α can be used as laboratory indicators to monitor clinical curative effect and evaluate prognosis of MS.

OBJECTIVETo study the anti-angiogenesis effect and toxicity of arsenic trioxide (As2O3) plus cinobufacin on transplanted human hepatocarcinoma in nude mice, and the acting mechanism of the treatment was explored as well.

METHODSHuman hepatocarcinoma was transplanted in nude mouse, and the modeled mice were divided at random into 4 groups, 8 in each group. They were treated respectively with normal saline (GA), 2.5 mg/kg As2O3 (GB), 5 mL/kg cinobufacin (GC) and 2.5 mg/kg As2O3 + 5 mL/kg cinobufacin (GD), by intraperitoneal injection for 21 days. The anti-tumor effects was evaluated by estimating general condition of nude mice, tumor size, microvessel density(MVD) level. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in tumor, in tumor tissue of mice as well as pathology of tumor were detected by immunohistochemistry assay, optical microscope, transmission electron microscope (TEM), respectively. Moreover, blood routine and pathological examinations of liver and kidney were performed.

RESULTSThe tumor weight and volume were 0.65 +/- 0.25 g and 0.44 +/- 0.14 cm3 in GB, 0.70 +/- 0.27 g and 0.46 +/- 0.19 cm3 in GC, 0.42 +/- 0.16 g and 0.26 +/- 0.11 cm3 in GD, all significantly lower than those in GA (1.06 +/- 0.25 g and 0.67 +/- 0.17 cm3, P < 0.05). The coefficient of drug interaction (CDI) on tumor weight was 0.97 and that on tumor size was 0.86, all less than 1, showing the synergistic action between the two drugs. Expressions of VEGF and EGFR in tumor as well as the MVD were decreased in GB and GC, and the decreasing of these indices were even more significant in GD. Pathologic examination showed the growth of tumor in GB, GC and GD were all inhibited significantly. No obvious toxicity of the treatments to the hepatic, renal and hematopoietic systems in the nude mice was observed.

CONCLUSIONSAs2O3 and cinobufacini showed synergistic action in inhibiting human hepatocarcinoma in nude mice and the angiogenesis in tumor. Combined use of the two had no obvious toxicity to the hepatic, renal and hematopoietic systems.

Amphibian Venoms ; pharmacology ; therapeutic use ; Angiogenesis Inhibitors ; Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; blood supply ; drug therapy ; Cell Line, Tumor ; Drug Synergism ; Humans ; Liver Neoplasms ; blood supply ; drug therapy ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; drug therapy ; Oxides ; pharmacology ; therapeutic use ; Phytotherapy ; Xenograft Model Antitumor Assays

Objective To examine whether the marginal division of the striatum(MrD)is involved in the associative learning and memory function of human brain with the help of functional magnetic resonance imaging(fMRI)technique.Methods Sixteen right-handed normal volunteers participated in a test of paired-word associative learning and memory,while the fMRI data were recorded.Control tasks were performed for the block-design.Statistcs parameter mapping 99 was used to analyze the data and to obtain the activated brain regions.Results When the threshold was set as P＜0.005.using a one-sample T-test,the left occipital lobe and the superior and middle gyrus of the left frontal lobe were activated remarkably during the encoding process of the paired-word associative learning and memory task,with the maximum intensity T value being 13.87 and 9.36.respectively.The left MrD was also obviously activated during this stage(T value was 5.46).But during the retrieval process,the left parietal lobe was prominently activated(T value was 8.73).Conclusion The resuhs of this study reveal that the subcortical structures such as MrD as well as the cerebral cortex are involved in the associative learning and memory of paired-word in human brain.

Objective To investigate the neural representations of long-term digital memory in human brain by functional magnetic resonance imaging (fMRI) technique. Methods 22 right-handed normal volunteers were recruited to participate in a test of long-term digital memory while the fMRI data were recorded. Control tasks were performed for the block-design. SPM 99 was used to analyze the data and to obtain the activated brain regions.Numbers of activated voxels were used to calculate lateralization index (LI). Results When the threshold was set as P＜0. 0001 ,using a one-sample t -test,the middle gyrus of the left frontal lobe(t=9.68) and the right cerebellum ( t = 9.85 ) were activated remarkably during the memory task. The subcortical structures including the thalamus (t=6.72) and the caudate (t=6.58) were also obviously activated during the memory task. LI of the numbers of activated voxels was 0.51. Conclusions The subcortical structures and the cerebellum as well as the cerebral cortex are collaborative to contribute to long-term digital memory function in human brain. The results also reveal that the functional areas of long-term digital memory in human brain are localized with the functional lateralization in the left hemisphere.

OBJECTIVETo explore clinical efficacy of Yiguanjian Decoction (YD) combined Adefovir Dipivoxil Tablet (ADT) in treating HBeAg negative chronic viral hepatitis B (CVHB) active compensated liver cirrhosis (LC) patients.

METHODSTotally 68 HBeAg negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group using random digit table, 34 in each group. Patients in the control group took ADT alone, 10 mg each time, once per day. Those in the treatment group additionally took YD, one dose per day. The therapeutic course for all was 48 weeks. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) were detected once in every two weeks. Hepatitis B virus (HBV)-DNA and four items of serum liver fibrosis [procollagen type I (PCN), hyaluronidase (HA), procollagen III peptide (PCIII), laminin (LN)] were detected once per every 4 weeks. Abdominal ultrasound B was performed before and after treatment. The inner diameter of the portal vein and the size of spleen were recorded. The fibrosis degree of liver was evaluated using Fibroscan. Efficacy of Chinese medicine (CM) was evaluated between the two groups before and after treatment using CM syndrome integrals. Efficacy of Western medicine (WM) was also evaluated between the two groups using Child-Pugh grading. Results Compared with before treatment in the same group, ALT and AST levels restored to normal levels, HBV-DNA turned negative (HBV-DNA < or = 1 x 10(2)) in the two groups after 48-week treatment. Besides, levels of TBil, ALB, PCIV, HA, PCIII, and LN obviously decreased (P < 0.05, P < 0.01). Results of ultrasound B showed the inner diameter of the portal vein and the size of spleen decreased. Fibroscan results showed that the elasticity value of the liver obviously decreased (P < 0.05). Besides, post-treatment levels of PCIV, HA, PCEJ, and LN, and the elasticity value of the liver decreased more obviously in the treatment group than in the control group (P < 0.01). There was no statistical difference in post-treatment levels of ALT, AST, TBil, ALB, inner diameter of the portal vein, or the size of spleen between the two groups (P > 0.05). Compared with before treatment in the same group, scores of Chinese medical syndrome and Child-Pugh scores decreased in the two groups after treatment (P < 0.05, P < 0.01). Besides, scores of Chinese medical syndrome decreased more obviously in the treatment group than in the control group (P < 0.05). The effective rate was 8824% (30/34) in the treatment group, higher than that of the control group [67.65% (23/34)] with statistical difference (P <0.05). Conclusion Combined treatment of YD and ADT could significantly improve symptoms of CM and fibrosis degree of liver of HBeAg negative CVHB active compensated LC patients.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; DNA, Viral ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Liver Cirrhosis ; drug therapy ; virology ; Organophosphonates ; therapeutic use ; Tablets

Objective To investigate the feasibility of ~1H-MR spectroscopy(~1H-MRS)imaging to quantitatively detect fatty liver.Methods Twenty patients with fatty liver and 11 healthy volunteers underwent plain CT scan,conventional MR imaging and ~1H-MRS analysis.The blood lipid and liver function were tested on the same day as the MR examination.~1H-MRS sequence measured the peaks of H_2O and lipid,and the areas under the peaks.The relative contents of the lipid compound were calculated,and compared with the results of CT scan and liver function tests.Results The CT values of the normal group and the fatty liver group were(59?9)HU and(24?11)HU respectively.On ~1H-MRS a protruding high H_2O peak and a flat low lipid peak were observed in the normal group,while the protruding high H_2O peak and a high lipid peak appeared in the fatty liver group.The values of lipid peak in the normal group and the fatty liver group were(0.05?0.01)?10~5,(0.70?0.24)?10~5 respectively(t=4.32,P0.05),the areas under the lipid peak were(1.36?0.73)?10~9、(2.35?1.15)?10~9 respectively(t=5.21,P0.05).Conclusion ~1 H-MRS imaging is feasible to quantitatively detect liver fat and is a non-invasive method for detecting early fatty liver.

Objective To detect the effective strategy for monitoring the early liver leisure.Methods Two grups,in- cluding clinical symptoms with ALT test and clinical symptoms with PA and ALT test,were used to monitor the liver leis- ure.Results There are 74% of cases founded occurring liver leisure during anti-tuberculosis therapy after administe- ring the latter strategy including clinical symptoms with PA and ALT test.The incidence of occurring liver leisure is 51% at one week,none of the defaults occurred after onset of drug induced liver leisure when they were administered the liver protection drugs,and the rate of treatment completion is 100%,only 27% of patients was detected with liver leisure after using the former strategy including clinical symptoms with ALT test.The incidence of liver leisure is 2% at one week,the frequency of discontinued therapy is 16% after on-set of drug induced liver leisure when they took the liver protecting drug,and the full-time therapy rate is 84%.Conclusion The indicator including clinical symptoms,PA and ALT is prospective strategy in monitoring liver leisure,which can be used to detect the early liver leisure effectively induced by anti-tuberculosis drugs.The anti-tuberculosis therapy can be introduced smoothly,and the incidence of treatment fail- ure will be decreased by using liver protection drug after onset of drug induced liver leisure.

AIMTo explore the effect of remodeling and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in spontaneously hypertensive rats.

METHODSThe spontaneously hypertensive rat(SHR) were given with BH4 chronically. The opening angle in the zero-stress state , wall-to-lumen area ratios (W/L) of thoracic aorta and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image analysis in 4, 16, and 26 week-old respectively.

RESULTSTreating with BH4 chronically from 4 weeks-old in SHR, there was a significant decrease in morphometric parameters of the thoracic aorta and an increase in the zero-stress state of opening angle of elastic artery. The P-D curve of mesenteric artery moved upward.

CONCLUSIONTreating with BH4 prevented the structure and function of artery from abnormal changing, including to attenuate the resistant vascular hypertrophy and recover the vascular elasticity and expansibility.

Animals ; Arteries ; physiopathology ; Arteriolosclerosis ; prevention & control ; Biomechanical Phenomena ; Biopterin ; analogs & derivatives ; therapeutic use ; Hypertension ; drug therapy ; physiopathology ; Male ; Nitric Oxide Synthase ; Random Allocation ; Rats ; Rats, Inbred SHR

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg^-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.