Research progress of long noncoding RNAs regulating human chondrocyte inflammatory signaling pathways in osteoarthritis / 中国药理学通报

Osteoarthritis is the commonest joint disease, but its etiology is still not clear.Recently the role of inflammation in its pathogenesis has been attached increasingly importance.Long noncoding RNAs (LncRNAs) play a key role in regulating the occurrence and development of inflammation-related diseases.This artiele reviews the research progress of LncRNAs in regula ting the occurrence and development of osteoarthritis through various endochondral inflammation signaling pathways in recent years , exploring the application of LncRNAs as a potential therapeutic target in the prevention and treatment of osteoarthritis.

Clinical features of panereatic disease-associated portal hypertension / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical features and management of pancreatic disease-associated portal hypertension.</p><p><b>METHODS</b>A retrospective analysis was carried out in patients with portal hypertension and concurrent pancreatic diseases. The medical records of these patients were reviewed including the data of demographics, etiologies, venous involvement, clinical presentations, laboratory tests, imaging studies, therapeutic modalities and outcomes.</p><p><b>RESULTS</b>Fifty-two patients with portal hypertension resulting from pancreatic diseases were found in our hospital, accounting for 4% of all the patients with portal hypertension in 11 years. The underlying pancreatic diseases were chronic pancreatitis (21 cases, 35.6%), pancreatic carcinoma (20 cases, 33.9%), acute pancreatitis (8 cases, 13.6%), pancreatic pseudocyst (3 cases, 5.1%). Of the 40 patients whose venous involvement was identified, splenic vein obstruction occurred in 27 cases (67.5%) and portal vein obstruction in 16 cases (40.0%). Mild or moderate splenomegaly was present in 48 cases (81.4%), with leukocytopenia as the most common manifestation of the 31 cases (52.5%) with concomitant hypersplenism. Forty-five patients (76.3%) developed gastroesophageal varices (including 35 with isolated gastricvarices), and among them 22 experienced bleeding (42.3%). Conservative treatment was effective in controlling acute bleeding, but could not prevent re-bleeding. Splenectomy was performed in 18 patients mainly due to gastrointestinal hemorrhage. No postoperative bleeding occurred during the follow-up ranging from 8 months to 9 years.</p><p><b>CONCLUSION</b>Pancreatic diseases may compromise portal vein and its tributaries, leading to generalized or regional portal hypertension. Pharmacological therapy can effectively control acute variceal bleeding, while surgical treatment is the appropriate procedure of choice in case of hemorrhagic recurrence.</p>

Toxicity of cationic liposome Lipofectamine 2000 in human pancreatic cancer Capan-2 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the toxicity of cationic liposome Lipofectamine 2000 (Lipo) in human pancreatic cancer Capan-2 cells.</p><p><b>METHODS</b>Capan-2 cells were cultured in the presence of Lipo at toxic concentrations, and the cell growth, apoptosis and cell cycle changes were evaluated by cell counting and flow cytometry.</p><p><b>RESULTS</b>The concentrations of both Lipo and siRNA affected the transfection efficiency. In a transfection volume of 2 ml, the presence of 5 microl Lipo resulted in slowed growth of Capan-2 cells, which was especially obvious after 3 days (P<0.001). Prolonged culture of the transfected cells caused significant increases in early apoptotic cells (P<0.05) and in the damaged or necrotic cells (P<0.001), and resulted in reduced viable cells (P<0.01); these changes became obvious after a 48-hour culture, which also increased the ratio of G(0)/G(1) phase cells (P<0.05) and decreased those of G(2)/M phase cells (P<0.01), S phase cells (P<0.01), and the late apoptotic cells (P<0.05).</p><p><b>CONCLUSION</b>Toxic concentrations of Lipo can affect the growth, apoptosis and cell cycles of Capan-2 cells in vitro, and this urges careful concentration selection when using Lipo for gene transfer into different cells.</p>

Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5-fluorouracil loaded polylactic acid nanoparticles / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice.</p><p><b>METHODS</b>Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed.</p><p><b>RESULTS</b>The tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti-VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05).</p><p><b>CONCLUSION</b>Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug.</p>

Biodistribution of (99m)Tc-labeled anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles in human gastric carcinoma xenografts / 南方医科大学学报

<p><b>OBJECTIVE</b>To prepare (99m)Tc-labeled Anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles ((99m)Tc-Ab-5-FU-NPs) and investigate its biodistribution in human gastric carcinoma xenografts.</p><p><b>METHODS</b>(99m)Tc-Ab-5-FU-NPs were prepared by labeling Ab-5-FU-NPs with (99m)Tc using improved Schwarz method. After isolation of (99m)Tc-Ab-5-FU-NPs using SephadexG250 column, the labeling ratio and radiochemical purity were determined using chromatography. The immunocompetence of (99m)Tc- Ab-5-FU-NPs was detected by ELISA and immunohistochemistry. (99m)Tc-Ab-5-FU-NPs were then injected via the tail vein into SCID mice bearing human gastric carcinoma, and (99m)Tc labeled mice-derived monoclonal IgG loaded polylactic acid nanoparticles were used as the control, followed by radioimmunoscintigraphic imaging at 2 and 6 h. The radioactive count and radioactive ratio of the tumor and non-tumor tissue (T/NT) in the animal models were calculated using ROI technique. After imaging at 24 h, SCID mice were sacrificed and the radioactive distribution, the %ID/g, as well as the T/NT radioactive ratio were examined, respectively. The concentrations of 5-FU in the tumor and blood were also detected using HPLC method.</p><p><b>RESULTS</b>The labeling ratio of (99m)Tc-Ab-5-FU-NPs was 90%-95%. (99m)Tc-Ab-5-FU-NPs were detected in the tumor tissues by radioimmunoimaging 2 h after the injection. ID%/g in the tumor tissues at 2 and 6 h were both significantly higher than that of the control group. Both the ID%/g in tumor tissues and radioactive ratio of tumor and blood at 6 h were higher than those at 2 h, and the concentration of 5-FU in experimental group increased continuously with time and was significantly higher than that in control group.</p><p><b>CONCLUSIONS</b>(99m)Tc-Ab-5-FU-NPs prepared in this study can meet the demands of radioimmunoimaging, and the anti-VEGF monoclonal antibody possesses reliable immune targeting ability. Six hours after injection, (99m)Tc-Ab-5-FU-NPs can specifically accumulate in the tumor tissues in human gastric carcinoma xenografts at high concentration.</p>

Relationship between COX-2 expression and clinicopathological features of colorectal cancers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyclo-oxgenase 2 (COX-2) is involved in prostaglandin synthesis in central nervous system, and it also plays a role in human carcinogenesis. Our purpose of this study is to investigate the COX-2 expression in different development stages of colorectal cancer, and to discuss the relationship between the gene expression and clinicopathological features of the cancer.</p><p><b>METHODS</b>COX-2 expression was examined by immunohistochemical staining in 76 surgical specimens of colorectal cancer (44 of advanced stage and 32 of early stage), thirty-three adenomas and 18 normal colonic mucosal tissues taken by endoscopic biopsy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to evaluate the relation of COX-2 to prognosis.</p><p><b>RESULTS</b>COX-2 expression, divided into 4 grades from "-" to "+++", is respectively 83.3%, 16.7%, 0% and 0% in normal colonic mucosal tissues; 12.1%, 42.4%, 36.4% and 9.1% in adenomas; 6.3%, 28.1%, 46.9% and 18.7% in early colorectal cancers (ECCs), and 6.8%, 20.5%, 18.2% and 54.5% in advanced colorectal cancers (CRCs). The differences in COX-2 expression between advanced CRCs and early colorectal cancers (ECCs) as well as between the advanced CRCs and adenomas were statistically significant (P < 0.01); but there was no significant difference between ECCs and adenomas. Kaplan-Meier survival analysis showed a significant difference in the survival curves between low high COX-2 groups (P < 0.05). Cox proportional hazards regression showed that COX-2 expression was related to poorer long-term outcome with a hazard ratio of 2.665 unadjusted for other variables (P < 0.05), and COX-2 expression was an independent risk factor of poor prognosis.</p><p><b>CONCLUSIONS</b>COX-2 expression is gradually up-regulated in the development from normal epithelium to adenomas and from ECCs to advanced CRCs. Alhough the COX-2 protein can not be regarded as a tumor marker to diagnose CRCs early, COX-2 expression can be regarded as an independent risk factor of poor prognosis for postoperative patients with advanced CRCs.</p>