China faces substantial drug abuse problems that appear to be worsening with time. Opiate dependence is a major threat to the public health and social security of China because of its devastating medical effects, its impact on risk for HIV/AIDS and criminal behaviors, low rates of recovery and high rates of relapse. There is an urgent need to implement MMT and other modern treatments for opiate dependence more widely in China.

The expression of AGE and RAGE is up-regulated in the small intestine and colon of diabetic rats. The increased AGE and RAGE levels may contribute to diabetic GI dysfunction.

Fibroblast growth factors (Fgfs) play important roles in the pattern formation of early vertebrate embryos. We have identified a zebrafish ortholog of human FGF17, named fgf17b. The first phase of fgf17b expression occurs in the blastodermal margin of late blastulae and in the embryonic shield of early gastrulae. The second phase starts after the onset of segmentation, mainly in the presomitic mesoderm and newly formed somites. Injection of fgf17b mRNA into one-cell embryos induces expression of the mesodermal marker no tail (ntl) and rescues ntl expression suppressed by overexpression of lefty1 (lft1). Overexpression of fgf17b dorsalizes zebrafish gastrulae by enhancing expression of chordin (chd), which is an antagonist of the ventralizing signals BMPs. In addition, overexpression of fgf17b posteriorizes the neuroectoderm. Simultaneous knockdown of fgf17b and fgf8 with antisense morpholinos results in reduction of chd and ntl. Knockdown of fgf17b can alleviate inhibitory effect of ectopic expression of fgf3 on otx1. These data together suggest that Fgf17b plays a role in early embryonic patterning. We also demonstrate that fgf17b and fgf8 have stronger mesoderm inducting activity than fgf3, whereas fgf17b and fgf3 have stronger activity in posteriorizing the neuroectoderm than fgf8. Like fgf8, activation of fgf17b expression depends on Nodal signaling.

Chronic pancreatitis is a fibrogenic disease. In autoimmune pancreatitis (AIP), a lymphoplasmacytic infiltration is followed by fibrosis. In vitro it has been shown that pancreatic stellate cells are transformed into proliferating myofibroblasts mainly by transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF). We studied the expression of these profibrotic cytokines, their receptors, and their cellular sources in AIP. Pancreatic tissues from 21 patients with AIP of different grades of severity were selected from a series of 52 AIP cases. Myofibroblasts (ie, activated pancreatic stellate cells), macrophages, lymphocytes, plasma cells, and the cytokines latency-associated peptide, a TGF-beta1 propeptide, TGF-beta receptor II (TGF-beta-RII), PDGF-B, and the alpha and beta isoforms of the PDGF receptor (PDGF-R alpha and PDGF-R beta) were identified immunohistochemically. Their expression and cellular distribution were related to the severity of AIP. In grade 1 and 2 AIP, macrophages and myofibroblasts expressing profibrotic cytokines and their receptors were found in periductal areas showing lymphoplasmacytic inflammation. In grade 3 AIP, there were numerous macrophages, myofibroblasts, and epithelial cells which were positive for latency-associated peptide, PDGF-B, TGF-beta-RII, PDGF-R alpha, and PDGF-R beta not only in periductal, but also in interlobular and intralobular areas. In grade 4 AIP, which is characterized by advanced fibrosis, cellularity and expression of cytokines and their receptors were greatly reduced. Our data indicate that in AIP the occurrence of myofibroblasts is intimately related to the presence of macrophages and lymphoplasmacytic cells. These cells and adjacent epithelial cells express profibrotic cytokines and their receptors, which are probably responsible for the initiation and maintenance of the fibrogenic process.

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Poly(ethylene glycol) (PEG), which is considered as a gold standard for surface modification of nanoparticles in biomedical applications, has been reported to encounter the accelerated blood clearance (ABC) phenomenon after repeated administration. Herein, as an ideal substitute for PEG, a zwitterionic peptide sequence of alternating negatively charged glutamic acid (E) and positively charged lysine (K) was designed as a good candidate for surface modification of nanoparticles without the ABC phenomenon in vivo. PEG-protected gold nanoparticles (AuNP-PEG) suffered from a serious ABC phenomenon with very fast blood clearance after repeated injection. Meanwhile, the plasma IgM and IgG levels were significantly increased after the repeated injection of AuNP-PEG. However, zwitterionic stealth peptide-protected gold nanoparticles (AuNP-EK10) could avoid the activation of the ABC phenomenon. The increase of IgM and IgG levels was not observed after the repeated injection of AuNP-EK10. More interestingly, compared to AuNP-PEG, more AuNP-EK10 could be accumulated in tumor tissues after repeated injection of the nanoparticles to tumor-bearing nude mice, which might be especially important for the design of drug nanocarriers in cancer therapy.

Data on morphological and biomechanical remodeling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days respectively. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cmH20. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner.