Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis.

OBJECTIVE: Vitamin D receptor (VDR) gene polymorphisms may be associated with the risk of OA, however, evidence for this is controversial. This meta-analysis aims to confirm whether VDR gene polymorphisms are associated with OA. METHODS: Meta-analyses on the association between OA and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allele and homozygote contrast and contrasts in the recessive and dominant models. Stratification analyses by different demographic regions (Europe vs Asian) were also performed and pooled odds ratios (ORs) were obtained using the random effects model if the results were heterogeneous. RESULTS: A total of 13 relevant studies involving OA patients (n = 2104) and controls (n = 2939) were included in the analysis. There were significant associations between VDR ApaI polymorphisms and OA in the Asian population (A vs a: OR= 1.16, 95% CI 1.02, 1.32, P = 0.025; AA vs Aa/aa: OR= 1.36, 95% CI 1.04, 1.77, P = 0.025; AA vs aa: OR= 1.35, 95% CI 1.00, 1.80, P = 0.047), but not in the whole population. There was also a statistically significant association between FokI polymorphism and OA (FF vs Ff/ff: OR= 0.65, 95% CI 0.44, 0.95, P = 0.024); however, this result was derived from only two studies. No significant associations were found between VDR TaqI and BsmI polymorphisms and OA. CONCLUSION: There are modest but statistically significant associations between VDR ApaI polymorphisms and the susceptibility of OA in the Asian population.

A Clinical Study on Gestational Diabetes Mellitus and the Hearing of Newborns.

OBJECTIVE: This study aimed to explore the impact of gestational diabetes mellitus (GDM) on the results of newborn hearing screening. METHODS: A total of 666 pregnant women who gave birth in the Obstetric Department of Sunshine Ronghe Hospital from August 2017 to May 2018 were randomly selected, and 69 of these pregnant women had GDM and were assigned into group 1 (excluding other diseases). The average age of these patients was 31.07 years. A further 597 pregnant women had no GDM and were assigned into group 2 (excluding other diseases). The average age of these patients was 30.02 years. The results of newborn hearing screening results in group 1 and group 2 were compared. RESULTS: Comparisons of abnormal hearing screening between 2 groups are significant different (P < 0.05). In the GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of > 0.05, and the difference was not statistically significant. In the non-GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of >0.05, and the difference was not statistically significant. CONCLUSION: GDM increases the incidence of abnormal hearing in newborns.

The current state of proteomics in GI oncology.

Proteomics refers to the study of the entire set of proteins in a given cell or tissue. With the extensive development of protein separation, mass spectrometry, and bioinformatics technologies, clinical proteomics has shown its potential as a powerful approach for biomarker discovery, particularly in the area of oncology. More than 130 exploratory studies have defined candidate markers in serum, gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years. We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

[The epidemiological and clinical characteristics of 1316 cases of acute pancreatitis in Guangdong region].

OBJECTIVE: To explore the clinical characteristics and pathogenetic patterns of acute pancreatitis (AP) in Guangdong region. METHODS: Analysis and summary of the clinical data of 1316 AP patients admitted into the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and the Guangdong Provincial People's Hospital between 1986 and 2005 were made. RESULTS: The AP rates among 1986 - 1990, 1991 - 995, 1996 - 2000, 2001 - 2005 year subsections were 0.19%, 0.36%, 0.54% and 0.71%, respectively. 60.48% of the cases was associated with biliary tract disease and the rest were related to hyperlipidemic, idiopathic and alcoholic factors. Epigastric pain was the predominant clinical manifestation, with or without radiating lumbar and back pain. Digestive manifestations such as nausea and vomiting appeared in most of the patients. Contrast-enhanced dynamic computed tomography was a precise imaging technique for diagnosis and severity grading as well as for complication detection. 1104 patients received nonoperative treatment (integrated traditional and western medicine) with 24 deaths. 212 patients received operative treatment with 48 deaths. CONCLUSIONS: The incidence of AP increased in the recent 20 years. The pathogenesis of AP is numerous and complicated, and biliary tract disease is still the main etiology. The imaging techniques are beneficial for early diagnosis and severity grading. Nonsurgical treatment integrating traditional and western medicine should be applied for early therapy. Strictly handling the indications for surgery, avoiding early surgery and rationally using endoscopic technique may help to gain satisfactory therapeutic efficacy.

Effects of sulfasalazine on biopsy mucosal pathologies and histological grading of patients with active ulcerative colitis.

AIM: To investigate the mechanisms of sulfasalazine (SASP) in the treatment of ulcerative colitis (UC). METHODS: Changes of pathological signs and histological grading of 106 patients with active UC were observed before and after the treatment with SASP, 1 g, thrice daily for 6 wk. RESULTS: The effect of SASP on the vasculitis in lamina propria was 48.2% and 17.4% in the mild active UC (P<0.001) and 68% and 26.7% in the moderate active UC (P<0.001) before and after treatment. Fibroid necrosis of vessel wall was found in one case of mild UC and two cases of moderate UC before treatment and was not found after treatment. No thrombosis was found in mild UC before and after treatment, while thrombosis was found in one case of moderate UC before treatment. The effect on mucosal glandular abnormality was 30.4% and 13.0% in mild UC (P<0.05), and 42% and 40% in moderate UC (P>0.05) before and after treatment. The rate of eosinophil infiltration was 98.2% and 80.4% in mild UC (P<0.01), and 100% and 91.1% in moderate UC (P<0.05) before and after treatment. The effect on crypt abscess was 21.4% and 4.4% in mild UC (P<0.05), and 48% and 13.3% in moderate UC (P<0.001) before and after treatment. The effect on mucosal pathohistological grading was 2.00+/-0.84 and 0.91+/-0.46 in mild UC (P<0.001), and 2.49+/-0.84 and 1.31+/-0.75 in moderate UC (P<0.001) before and after treatment. CONCLUSION: SASP can improve small vessel lesions and crypt abscesses and reduce neutrophilic and eosinophilic leukocyte infiltration in inflammatory mucosa of UC.

Clinical features and risk factors of patients with fatty liver in Guangzhou area.

AIM: There is still no accepted conclusion regarding the clinical features and related risk factors of patients with fatty liver. The large-scale clinical studies have not carried out yet in Guangzhou area. The aim of the present study was to investigate the clinical features and related risk factors of patients with fatty liver in Guangzhou area. METHODS: A total of 413 cases with fatty liver were enrolled in the study from January 1998 to May 2002. Retrospective case-control study was used to evaluate the clinical features and related risk factors of fatty liver with logistic regression. RESULTS: Obesity (OR: 21.204), alcohol abuse (OR: 18.601), type 2 diabetes mellitus (OR: 4.461), serum triglyceride (TG) (OR: 3.916), serum low-density lipoprotein cholesterol (LDL-C) (OR: 1.840) and fasting plasma glucose (FPG) (OR: 1.535) were positively correlated to the formation of the fatty liver. The levels of serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) increased mildly in the patients with fatty liver and were often less than 2-fold of the normal limit. The higher abnormalities of aspartate aminotransferase (AST) levels (42.9%) with AST/ALT more than 2(17.9%) were found in patients with alcoholic fatty liver (AFL) than those with nonalcoholic fatty liver (NAFL) (16.9% and 5.0% respectively). The elevation of serum TG, cholesterol (CHOL), LDL-C was more common in patients with NAFL than with AFL. CONCLUSION: Obesity, alcohol abuse, type 2 diabetes mellitus and hyperlipidemia may be independent risk factors of fatty liver. The mildly abnormal hepatic functions can be found in patients with fatty liver. More obvious damages of liver function with AST/ALT usually more than 2 were noted in patients with AFL.

Clinical analysis of primary small intestinal disease: A report of 309 cases.

AIM: To evaluate the major clinical symptom, etiology, and diagnostic method in patients with primary small intestinal disease in order to improve the diagnosis. METHODS: A total of 309 cases with primary small intestinal disease were reviewed, and the major clinical symptoms, etiology, and diagnostic methods were analyzed. RESULTS: The major clinical symptoms included abdominal pain (71%), abdominal mass (14%), vomiting (10%), melaena (10%), and fever (9%). The most common disease were malignant tumor (40%). diverticulum (32%) and benign tumor (10%). Duodenal disease was involved in 36% of the patients with primary small intestinal diseases. The diagnostic rate for primary small intestinal diseases by double-contrast enteroclysis was 85.6%. CONCLUSION: Abdominal pain is the most common clinical symptom in patients with primary small intestinal disease. Malignant tumors are the most common diseases. Duodenum was the most common part involved in small intestine. Double-contrast enteroclysis was still the simplest and the most available examination method in diagnosis of primary small intestinal disease. However, more practical diagnostic method should be explored to improve the diagnostic accuracy.

Relationship between COX-2 expression and clinicopathological features of colorectal cancers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Knockdown of hTERT by SiRNA suppresses growth of Capan-2 human pancreatic cancer cell via the inhibition of expressions of Bcl-2 and COX-2.

OBJECTIVE: To investigate the effects of human telomerase reverse transcriptase (hTERT) on the growth of Capan-2 human pancreatic cancer cell and apoptosis. METHODS: Cell proliferation, apoptosis and cell cycle were analyzed by cell counting and flow cytometry. mRNA and protein expressions of hTERT, Bcl-2 and cyclooxygenase (COX)-2 were assessed by real time PCR and Western blot. RESULTS: Cell growth was significantly inhibited by 26.39 percent 24 h after hTERT-small interference RNA (siRNA) transfection (50 nmol/L) with a 100 percent silencing efficiency (P < 0.05). The inhibition rates of cell proliferation were 46.77 percent, 70.61 percent, 84.71 percent and 85.99 percent at 2, 3, 5 and 7 days after transfection, respectively (P < 0.001). Early and late apoptotic cells increased significantly (especially 24 h after transfection) (P < 0.001). The cell cycle was suppressed significantly as manifested by the increase of cells in the G0/G1 phase and the decrease of cells in the S phase and G2/M phase (P < 0.01). The expressions of Bcl-2 mRNA and COX-2 mRNA were inhibited significantly 48 h after transfection: the inhibition rates were 86.86 percent and 100 percent, respectively (P < 0.001). Levels of Bcl-2 protein were downregulated by 58.54 percent and 63.44 percent and the levels of COX-2 protein were downregulated by 50.06 percent and 82.77 percent at 48 h and 72 h after transfection, respectively. CONCLUSION: Knockdown of hTERT by siRNA can inhibit the growth of Capan-2 cell. The inhibitory effect is associated with the downregulation of Bcl-2 and COX-2.

[Clinical features of panereatic disease-associated portal hypertension].

OBJECTIVE: To investigate the clinical features and management of pancreatic disease-associated portal hypertension. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Toxicity of cationic liposome Lipofectamine 2000 in human pancreatic cancer Capan-2 cells].

OBJECTIVE: To investigate the toxicity of cationic liposome Lipofectamine 2000 (Lipo) in human pancreatic cancer Capan-2 cells. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Detection of intracellular and extracellular cytokines of CD4+CD25+ regulatory T cells in gastric cancer patients].

BACKGROUND & OBJECTIVE: CD4+CD25+ regulatory T cells play a crucial role in the immunosuppression of gastric cancer patients, but the mechanism is still unknown. This study was to investigate the secretion of intracellular and extracellular cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10 and tumor growth factor-beta (TGF-beta) from CD4+CD25+ regulatory T cells in gastric cancer patients, and evaluate their roles in the immunosuppression of gastric cancer. METHODS: Peripheral blood mononuclear lymphocytes of gastric cancer patients were prepared routinely. CD4+CD25+ T cells and CD4+CD25- T cells were isolated by magnetic activated cell sorting (MACS) method, and identified by flow cytometry. The cytokine secretion of CD4+CD25+ T cells and CD4+CD25- T cells was detected by intracellular analysis of cytokine production (IFN-gamma, IL-4 and IL-10) and ELISA (IFN-gamma, IL-10 and TGF-beta). RESULTS: The proportion of CD4+CD25+ T cells to CD4+ T cells was significantly higher in gastric cancer patients than in healthy controls (P<0.05). After 96-hour cell culture, no matter in gastric cancer patients or in healthy controls, the secretion of IL-10 and TGF-beta were significantly higher from CD4+CD25+ T cells than from CD4+CD25- T cells (P<0.05), but the secretion of IFN-gamma was significantly lower from CD4+CD25+ T cells than from CD4+CD25- T cells (P<0.05). CONCLUSION: The immunosuppression of CD4+CD25+ regulatory T cells in gastric cancer may relate to suppressive cytokines, especially TGF-beta.

[Endoscopic, clinicopathologic and immunohistochemical features of gastric stromal tumor].

BACKGROUND & OBJECTIVE: For gastric stromal tumor (GST), the low incidence and high diversity in endoscopic and pathologic manifestations lead to misdiagnosis. This study was to explore the features of GST in endoscopy and clinicopathology. METHODS: Clinical data of 42 GST patients, treated at the Second Affiliated Hospital of Sun Yat-sen University from Jan. 1996 to Jan. 2006, were analyzed for their clinicopathologic and endoscopic features. The expression of CD117, CD34, smooth muscle actin (SMA), Desmin and S-100 were detected by immunohistochemistry. Their correlations to clinicopathologic features of GST were analyzed. RESULTS: Of the 42 cases of GST, 21 (50.0%) were at the fundus, 14 (33.3%) at the body, and 7 (16.7%) at the antrum; 17 (40.5%) were benign, 14 (33.3%) borderline, 11 (26.2%) malignant. Endoscopically, GST presented submucosal hemispheroid or polypoid protuberant lesions with clear border. While the positive rate of gastroendoscopic biopsy was low. Of the 42 cases, 29 were spindle cell type, 5 were epithelial cell type, and 8 were mixed type. The positive rates of CD34 and CD117 were 92.86% and 78.57%. CONCLUSIONS: GST has unique morphologic features. Combined detection of CD117 and CD34 benefits the diagnosis of GST.

[Biodistribution of (99m)Tc-labeled anti-VEGF mAb 5-FU loaded polylactic acid nanoparticles in human gastric carcinoma xenografts].

OBJECTIVE: 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. METHODS: (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. RESULTS: 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. CONCLUSIONS: (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.

[Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5-fluorouracil loaded polylactic acid nanoparticles].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Preparation and release efficiency of polylactic acid nanoparticle].

BACKGROUND & OBJECTIVE: As a new drug delivery carrier, medical nanoparticle (NP) appears to be very promising and are widely studied. Compare with microparticle, nanoparticle possesses several advantages, such as ultramicroscopic size, could be ingested by the cells after crossing the tissue matrix, and can penetrate the arterial wall and cross the blood-brain barrier. This study was to prepare polylactic acid (PLA) nanoparticle, and observe its morphology, diameter, structure, surface elements, and ability of in vitro drug release. METHODS: The biodegradable PLA was used as the carrier, and 5-fluorouracil (5-FU) was used as the model drug. 5-FU-PLA nanoparticle (5-FU-PLA-NP) was prepared by matrix and ultrasound emulsification. Morphology of 5-FU-PLA-NP was observed under scanning electron microscope; its surface elements were detected by X ray photoelectron spectroscopyû its drug loading (DL), embedding ratio (ER), and ability of in vitro drug release were assessed by ultraviolet spectroscopy. RESULTS: The nanoparticle was uniformly spherical with average diameter of (191+/-17) nm, DL of 15.2%, and ER of 45.6%. The nanoparticle showed sustained release character in the experiment of in vitro drug release: the cumulative drug release rate in analog body fluid was 94.3% at the 10th day. CONCLUSION: PLA-NP may serve as a carrier of 5-FU, and can change the pharmacokinetics of 5-FU, slower down drug release; 5-FU-PLA-NP can be prepared as intravenous injection, and may prolong the in vivo circulation time of 5-FU, so as to play more efficient antitumor effects.