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Objective To investigate the intervention effect of GDC-0449, a hedgehog signaling pathway inhibitor, on rats with liver fibrosis induced by carbon tetrachloride (CCl 4 ) combined with 2-acetylaminofluorene (2-AAF). Methods A total of 18 female Fisher344 rats were randomly divided into normal group, CCl 4 /2-AAF group, and GDC-0449 group, with 6 rats in each group. The rats in the CCl 4 /2-AAF group and the GDC-0449 group were given subcutaneously injected 30% CCl 4 -olive oil solution at a dose of 2 mL/kg twice a week for 6 weeks to induce liver fibrosis; since week 7, in addition to the injection of CCl 4 -olive oil solution, the rats in these two groups were given 2-AAF (100 mg/kg/d) by gavage, and the rats in the GDC-0449 group were given GDC-0449 (25 mg/kg/d) by gavage, while those in the normal group were given an equal volume of olive oil solution by injection and normal saline by gavage. All rats were sacrificed at the end of week 9, and related samples were collected. HE staining and sirius red (SR) staining were used to observe the changes in liver histopathology and collagen deposition, and the semi-quantitative analysis of SR-positive area and Ishak score were used to evaluate fibrosis degree; the alkaline hydrolysis method was used to measure the level of hydroxyproline (Hyp) in liver tissue; immunohistochemistry, Western blot, and qRT-PCR were used to measure the expression of α-smooth muscle actin (α-SMA), type Ⅰ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ), cytokeratin 19 (CK19), cytokeratin 7 (CK7), the epithelial cell adhesion molecule Epcam, and the hedgehog signaling pathway in liver tissue; double immunofluorescence staining was used to observe the colocalization of CK19 and the oval cell marker OV6. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the CCl 4 /2-AAF group had marked inflammatory cell aggregation and collagen deposition in liver tissue, with the formation of a pseudolobular structure, as well as significant increases in Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Col-Ⅰ, Col-Ⅳ, Epcam, CK19, CK7, the transmembrane transporter Smoothened (Smo), Hedgehog ligand Desert Hedgehog (Dhh), the Indian Hedgehog membrane-binding receptor Patched (Ptch2), and glioma-related oncogenes Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed that CK19-positive cells also expressed OV6 in the liver tissue of rats in the CCl 4 /2-AAF group, with a significant increase compared with the normal group. Compared with the CCl 4 /2-AAF group, the GDC-0449 group had significant reductions in inflammatory cell aggregation and collagen deposition in liver tissue, Hyp level and collagen positive area ratio in liver tissue ( P < 0.05), Ishak score ( P < 0.05), and the expression of α-SMA, Epcam, CK19, CK7, Smo, Ptch2, Gli1, Gli2, and Gli3 (all P < 0.05); double immunofluorescence staining showed a significant reduction in the number of cells with co-expression of OV6 and CK19 in liver tissue. Conclusion The Hedgehog signaling pathway inhibitor GDC-0449 can significantly inhibit the progression of liver fibrosis induced by CCl 4 /2-AAF in rats, possibly by inhibiting hepatic stellate cell activation, collagen deposition, activation and proliferation of hepatic progenitor cells, and differentiation of hepatic progenitor cells into biliary epithelial cells.
ABSTRACT
@#In the context of the global pandemic of COVID-19, with the epidemic epicenter located in the Wuhan City, China, patients with severe mental illness have also been deeply affected by the epidemic. In this paper, two patients with schizophrenia who recovered from COVID-19 were reported. Because of the long-term positive results of the SARS-CoV-2 serum antibody IgM test, they had to undergo medical isolation and social restrictions for a long time. After the situation was effectively identified by the medical staff and they were eliminated as a potential virus carrier and released from the medical isolation center. Since psychiatrists often lack systematic knowledge of infectious diseases, the authors hope that this paper can provide a reference to avoid unnecessary wastage of medical resources and prevent placing serious mental burden on such patients in the future.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical curative effect of the modified Halo pelvic frame and surgery for the treatment of severe scoliosis with rigidity.</p><p><b>METHODS</b>From January 2004 to May 2010,50 patients with severe scoliosis patients with rigidity were treated in our hospital. Twenty-three patients were male and 27 patients were female, with a mean age of 10.8 years old, ranging from 4 to 16 years. Twenty-four patients were congenital scoliosis and 26 patiens were idiopathic scoliosis. The mean body height were (152.1 +/- 11.1) cm and the average Cobb angle of scoliosis and kyphosis were (91.8 +/- 14.5) degrees and (69.5 +/- 14.0) degrees respectively. All the patients were treated with three-stages modified Halo pelvic traction, the second stage anterior release and the third stage posterior correction. The amount of correction was determined by measuring the change of body height, the Cobb angles and correction rate of scoliosis as well as kyphosis before and after the operation.</p><p><b>RESULTS</b>The mean body height were correct to (158.5 +/- 10.5) cm. The average Cobb angle of scoliosis were correct to (30.8 +/- 7.9) degrees. The average Cobb angle of kyphosis were correct to (31.6 +/- 10.1) degrees. After the first stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean of (30.4 +/- 6.6)% correction and (22.3 +/- 5.2)% respectively; after the second stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean (26.7 -/+ 5.1)% correction and (21.2 -/+ 6.0)% respectively; the third stage, above data were (33.7 -/+ 7.2)% and (27.1 +/- 5.3)%. Correction rate of scoliosis and kyphosis were (66.5 +/- 7.2)% and (55.1 +/- 6.4)% respectively by the modified Halo pelvic frame traction and surgery. Body height, the Cobb angles and correction rate of scoliosis and kyphosis on radiographs were different in all stages (P<0.05).</p><p><b>CONCLUSION</b>Operative complications of severe scoliosis with rigidity can be reduced and better deformity correction and trunk balance achieved by the modified Halo pelvic frame traction and surgery.</p>