Objective To investigate the protective effect of Gingko Biloba extract (GBE) on acute lung hemorrhage induced by Lipopolysaccharide(LPS) in newborn rats. Methods 1. Acute lung hemorrhage models were reproduced by intraperitoneal injection with LPS (5 mg/kg). 2. Thirty two rats were randomly divided into 4 groups,GBE groups (4 mg/kg,8 mg/kg, 16 mg/kg) and LPS group 5 mg/kg. Results In group LPS, extensive lung hemorrhage was observed after 4 hours of injection . TNF - ? iung content was obvious in LPS group. The expression of lung nuclear factor(NF-kB )immunohistochemistry wasobvious. While the parameters were obviously attenuated by GBE before LPS. Conclusion GBE may be useful in the treatment of acute pulmonary inflammatory disease.

This study was to investigate the permeability and absorbability of capsaicin cubosome across abdominal skin of the SD rats in vitro. Diffusion of capsaicin cubosome and cream was performed with the modified Franz diffusion cell technique. The capsaicin cubosome showed no enhancement of skin permeation within 24 hours. However, the deposition amounts of capsaicin in the rat skin in the cubosome group was markedly higher than those in the commercial cream group (P < 0.01). Cubosome showed excellent characetristic of skin-targed which could be a good carrier for the local transdermal drug delivery system.
Administration, Cutaneous ; Animals ; Capsaicin ; administration & dosage ; chemistry ; Kinetics ; Male ; Particle Size ; Permeability ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; Skin Absorption

Objective To investigate the effect of cyaniding?3?glucoside (Cy3G) on glucose and lipid metabolism in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease (AD). Methods Seven?month?old APPswe/PS1ΔE9(PAP) mice were randomly divided into model group (PAP), Cy3G treatment group (PAPCy, 5 mg/kg/d) and negative?control group (nPAP). In addition, age?matched and normal wild?type of C57BL/6J mice were selected and divided into vehicle group (WT), Cy3G intervention group (WTCy, 5 mg/kg/d). Each group containing 12 mice, with equal number of male and female mice. After 8?week Cy3G supplementation, microPET/CT was used to measure cerebral glucose metabolism rate of mice in each group. Biochemical methods were used to detect the liver / kidney function as well as indicators associated with lipid metabolism. After weighting brain tissue, the brain coefficient was tested and pathological examination was used to observe tissues changes. Transmission electron microscope was used to observe neuropathological amyloid plaques deposition. Western?blot was used to determine protein levels of AKT and JNK. Results Compared with the WT group, PAP mice had low levels of 18 F?FDG uptake rates, especially in the regions of the frontal lobe and hippocampus accompanied by the decreased brain coefficient and amyloid plaques deposition in hippocampus. And levels of aspartate transaminase ( AST) and lactic dehydrogenase ( LDH) were also increased in PAP mice, but lipid metabolism index was relatively normal. In addition, the expression of JNK was decreased and AKT was increased in mice of PAP. However, in the PAPCy group, 18 F?FDG uptake rates were obviously increased in the regions of the frontal lobe and hippocampus compared with those in the PAP mice. And the reduction of brain atrophy and amyloid plaques deposition, normal lipid metabolism and no obvious liver/kidney toxicity were also observed. Cy3G also could reverse the changes of JNK and AKT protein. Conclusions Cy3G can improve glucose metabolism disorders instead of lipid metabolism, inhibit the senile plaques deposition in hippocampus and regulate insulin resistance and inflammatory reaction associated with JNK/AKT pathway. Thus, Cy3G has a good safety profile and may be used as an ideal alternative to traditional disease?modifying treatments against AD.

Objective: To investigate the effects of oxLDL and HMG-CoA reductase inhibitor simvastatin on PKC activity, and level of cytosol ic free Ca 2+ in cultured human umbilical vein endothelial cells. Methods: Th e activity of PKC was determined by its ability to transfer phosphate from 32P-ATP to lysine-rich histone and level of cytosolic free calcium［Ca2+ ］i was measured by flow cytometric analysis loading with the Ca2+ dye F luo-3/Am. Results: oxLDL increased PKC total activity in a dose-de pendent manner and peaked after 12 min, then decreased slowly and maintained for at least 30 min, while oxLDL induced biphasic ［Ca2+］i responses includ ing the rapid initial transient phase and the sustained phase. Removal of extrac ellular Ca2+ did not inhibit the rapid transient phase, but abolished the sustained phase. When simvastatin was added, the activity of PKC wasmarkedly dec reased with no impairment to the initial peak response, but significantly reduce d the sustained phase. Conclusion: oxLDL can induced dynamic changes of signal transduction of PKC and level of cytosolic free Ca2+ in HUVEC, these 2 events are closely linked. The change of rapid initial transient phase i s the result of mobilization of Ca2+ from intracellular pool and the chang e of sustained phase is from the influx of extracellular Ca2+. The inhibit ion of PKC activity induced by simvastatin may contribute to the changes of ［Ca 2+］i.

OBJECTIVETo investigate whether the serum levels of inflammation-related cytokines might be different between the healthy individuals and the psoriatic patients diagnosed of three varied Chinese medicine (CM) syndromes [blood-stasis syndrome (BSS), blood-dryness syndrome (BDS) and wind-heat syndrome (WHS)].

METHODSA total of 62 psoriatic patients were recruited and assigned to 3 groups according to their CM syndromes, including 27 patients of BSS, 21 of BDS and 14 of WHS. Another 20 sex- and age-matched healthy subjects were enrolled into the control group. Serum concentrations of multiple cytokines, including monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), soluble CD4O ligand (SCD40L), tumor necrosis factor-α (TNF-α), epidermal growth factor (EGF), interleukin-8 (IL-8), interleukin-17 (IL-17), interferon γ inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF), were measured by a multiplexed flow cytometric assay.

RESULTSThe circulating levels of MIP-1α, TNF-α, IL-8, and IP-10 were significantly increased in the psoriatic patients compared with the healthy controls (P<0.01). Male and female patients tended to have higher serum levels of MCP-1 and IP-10, respectively (P<0.05). Interestingly, compared with the control group, 6 out of the 9 cytokines (MCP-1, MIP-1α, TNF-α, EGF, IL-8 and IP-10) were substantially increased in the BSS group (P<0.05 or P<0.01), whereas only MIP-1α and IL-8 levels were elevated in the BDS group (P<0.05 or P<0.01) concurrent with lowered concentrations of SCD40L and IL-17 (P<0.05). In the WHS group, MIP-1α was the only cytokine whose level was evidently increased (P<0.01), in contrast to IL-17 which was decreased as compared with the control (P<0.05). The psoriatic patients overall owned higher levels of MIP-1α and IL-8 in the circulation which were comparable among the 3 groups of CM syndromes (P<0.01). In contrast, TNF-α level of the BSS group was the highest among the three (P<0.01), followed by the BDS and the WHS groups.

CONCLUSIONSThe expression profiles of cytokines in the circulation might not be necessarily identical for psoriatic patients with different CM syndromes. Accordingly, the serum concentrations of certain cytokines could potentially be used as the ancillary indices for the clinical classification of psoriatic CM syndromes.

Adult ; Aged ; Case-Control Studies ; Cytokines ; blood ; Female ; Humans ; Inflammation Mediators ; blood ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Psoriasis ; blood ; Severity of Illness Index ; Statistics, Nonparametric ; Syndrome ; Young Adult

OBJECTIVETo evaluate the value of positron emission tomography (PET) in diagnosing liver metastases from colorectal cancer.

METHODSEighteen patients suspected with liver metastases after resection of colorectal cancer and three patients suspected with other diseases were diagnosed by PET and CT before operation. The result of both diagnostic approaches was compared with the result of exploratory operation.

RESULTSSeventeen of 18 patients were confirmed as liver metastases after resection of colorectal cancer, in whom 14 patients had other synchronous metastases outside liver metastasis including lung metastasis (n= 2), abdominal wall metastasis (n= 2 ), bone metastasis (n= 1), peritoneal cavity lymph nodes metastasis (n= 6), mediastinal lymph nodes (n= 2), virchow lymph node metastasis (n= 1). One patient with negative PET diagnosis was still alive with cancer- free after 1 year followed- up. Three patients suspected with other diseases were also diagnosed as liver metastases from colorectal cancer by PET.

CONCLUSIONPET has higher sensitivity in diagnosing liver metastases or other synchronous metastases after resection of colorectal cancer, which suggests that PET can guide the determination of second operative surgery for liver metastases after resection of colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; pathology ; Female ; Humans ; Liver Neoplasms ; diagnostic imaging ; secondary ; Lymphatic Metastasis ; diagnostic imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Sensitivity and Specificity ; Tomography, X-Ray Computed

[Objective]To study the intervention effect of mild hypotherrnia on cerebral edema in rats after cerebral infarction.[Methods]Twelve male SD rats were randomized into control group (n--6) and mild hypotherma treatment group (n=6).The rat models of focal cerebral infarction were established with obstructing the middle cerebral artery of rats by suture emboli.Rats of the mild hypotherma treatment group were treated by mild hypotherm for 3 h after the models were established.MRI was performed at 6 h,and 1,3,5 and 7 d after the success of model making.Cerebral infarction volume,absorption rate of edema,and signal intensity ratios (SIRs) ofTIWl,T2WI,FLAIR and DWI sequencas in the infarction zones,and relative variance ratio of SIR (△SIR) were measured and calculated.[Results] In the mild hypotherma treatment group,the cerebral infarction volumes 3,5 and 7 d after the models were established were significantly decreased as compared with those in the control group (P＜0.05);the absorption rate of edema (the 7th d against the 3th d of infarction) in the the mild hypotherma treatment group was significantly higher than that in the control group (P＜0.05).Three,5 and 7 d after infarction,the SIRs of TIWI were all obviously higher than those in the control group,and the SIRs of T2WI and FLAIR were all significantly lower than those in the control group (P＜0.05).The SIR of DWI in the mild hypotherma treatment group was obviously lower than that in the control group 7 d after infarction (P＜0.05).The △SIRs of T2Wl,FLAIR and DWI in the mild hypotherma treatment group were significantly higher than those in the control group (P＜0.05).[Conclusion] Mild hypothermia has a significant inhibition effect on cerebral edema in rats after cerebral infarction.

Background: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree. Methods: We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease?related gene panel containing 519 genes associated with genetic myopathy (including 17 CMS genes). Results: In the family, the proband showed limb?girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband's two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation (c.5302G>C, p.A1768P) of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions: This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb?girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.

BACKGROUNDKCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes.

METHODSWe studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects.

RESULTSrs5219 (E23K) in KCNJ11 was associated with genetic susceptibility to type 2 diabetes (OR = 1.400 with 95% CI 1.117 1.755, P = 0.004 under an additive model, OR = 1.652 with 95% CI 1.086 2.513, P = 0.019 under a recessive model, and OR = 1.521 with 95% CI 1.089 2.123, P = 0.014 under a dominant model) after adjusting for sex and body mass index (BMI). We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 (Pro12Ala) and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion (P = 0.005) after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin (P = 0.004 under an additive model for rs2144908; and P = 0.001 under a dominant model for rs2144908) after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala.

CONCLUSIONSOur study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.

ATP-Binding Cassette Transporters ; genetics ; Adult ; Body Mass Index ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Hepatocyte Nuclear Factor 4 ; genetics ; Humans ; Male ; Middle Aged ; PPAR gamma ; genetics ; Polymorphism, Single Nucleotide ; genetics ; Potassium Channels, Inwardly Rectifying ; genetics ; Receptors, Drug ; genetics ; Sulfonylurea Receptors

OBJECTIVETo evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).

METHODSFrom September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.

RESULTSResponse in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.

CONCLUSIONSThe combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Drug Administration Schedule ; Epirubicin ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives