BACKGROUNDProbucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis.

METHODSAortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks' atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed.

RESULTSProbucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group (56% vs. 21%, 18% vs. 54%, respectively, both P < 0.01). In addition, the probucol group showed a smaller mean remodeling index relative to the control group (0.93 ± 0.13 vs. 1.05 ± 0.16, P < 0.01). Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S (all P < 0.01).

CONCLUSIONSThese findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.

Animals ; Anticholesteremic Agents ; pharmacology ; Aorta ; pathology ; Apoptosis ; drug effects ; Atherosclerosis ; drug therapy ; metabolism ; pathology ; Lipids ; blood ; Macrophages ; drug effects ; physiology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Oxidative Stress ; Probucol ; pharmacology ; Rabbits ; Ultrasonography, Interventional ; methods

· AIM:To study whether autophagy and paraptosis were activated in retinal ganglion cells (RGCs) after acute high intraocular pressure (lOP) in an experimental rat model and to explore the possible underlying mechanisms.· METHODS:A total of 50 male Sprague-Dawley (SD)rats were randomly divided into normal control group,and 3d,1,4,8wk group after acute elevated intraocular pressure(IOP) (n =10 per group).Acute intraocular hypertension model was established by anterior chamber perfusion of normal saline in the right eye.The expression levels of microtubule-associated protein 1 light chain 3 (LC3) was measured by immumofluorescence method.To determine whether autophagy and paraptosis were activated.Retinal sections were examined by transmission electron microscopy (TEM).Autophagosomes and cytoplasmic vacuoles in the cytoplasm of RGCs were measured.· RESULTS:TEM analysis revealed that double-and multiple-membrane vacuoles containing electron-dense materials of autophagosomes were found in RGCs.The number of autophagosomes per 50μ m2 were 0.79 ± 0.43,2.14±0.36,2.29±0.47,1.57±0.51 and 1.21±0.43 in the normal control group and in acute IOP group at 3d,1wk,4wk,8wk,respectively.The number of autophagosomes markedly increased in the cytoplasm of RGCs at 3d,1wk,4wk,8wk groups than those in the normal control group (all at P＜ 0.05).LC3 positive expression was rarely detected in ganglion cell layer (GCL) in the normal control group and percentage of LC3 positive cells was 15.90％.Immumofluorescence analysis showed that the percentage of LC3 positive cells statistically increased in acute lOP groups when compared with control group (P＜0.05).The number of RGCs per 200μm in each group of acute lOP injury significantly decreased compared with the normal control group (P ＜ 0.05).Cytoplasmatic vacuolization were observed in RGCs at 3d after acute lOP injury and lasting to 8wk.TEM also revealed that a large number of cytoplasmic vacuoles were derived predominantly from the progressive swelling of mitochondria and/or endoplasmic reticulum (ER).· CONCLUSION:Autophagy and paraptosis participate in the death of RGCs under transiently elevated intraocular pressure.Different types of programmed cell death (PCD),coexistence of multiple cell death forms or a single cell death form,participates in the pathogenesis of acute elevation of intraocular pressure.

OBJECTIVETo evaluate safety and efficacy of preoperative administration of enteral nutrition support in gastric cancer patients at risk of malnutrition.

METHODSA single center randomized controlled clinical trial was performed in 60 gastric cancer patients in West China Hospital from May to October 2012. Thirty patients were given enteral nutrition support(Ensure(R)) manufactured by Abbott Laboratories for ten consecutive days before surgical operation in the treatment group, and 30 patients were given an isocaloric and isonitrogenous homogenized diet in the control group for 10 days as well. The laboratory parameters of nutritional status and hepatorenal function were observed and compared between the two groups on admission, preoperative day 1 and postoperative day 3, respectively. Clinical observations, such as nausea and vomiting, were carried out until patients were discharged.

RESULTSBefore the intervention, there were no significant differences in the baseline characteristics between the two groups. The levels of serum albumin [(33.9±5.6) g/L vs. (31.0±5.3) g/L, P<0.05], and hemoglobin[(103.4±7.7) g/L vs.(96.6±10.5) g/L, P<0.01] were significantly improved in the treatment group on postoperative day 3. However, the levels of body mass index, lymphocyte count, liver and renal function, serum glucose, sodium, and potassium were not significantly different between the two groups(all P>0.05). Moreover, two patients with nausea and one with vomiting in each group were found. In clinical observation period, no severe treatment-related adverse event were observed.

CONCLUSIONThe enteral supplement with Ensure(R) in gastric cancer patients at risk of malnutrition during preoperative period is effective and safe, which is superior to homogenized diet and an appropriate choice for gastric cancer patients with nutritional risk.

Enteral Nutrition ; Gastrectomy ; adverse effects ; Humans ; Malnutrition ; etiology ; prevention & control ; Nutritional Status ; Postoperative Period ; Preoperative Care ; methods ; Risk Factors ; Stomach Neoplasms ; surgery

OBJECTIVETo investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC).

METHODSTwo-hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis.

RESULTS(1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05).

CONCLUSIONSAnalysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more.

Adenocarcinoma, Mucinous ; drug therapy ; metabolism ; pathology ; surgery ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Grading ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo study the effects of lysyl oxidase (LOX) on the migration and adhesion of the human gastric cancer cell line HGC-27 cells in vitro.

METHODSThe human gastric cancer cell line HGC-27 cells were cultured in vitro, and treated with different concentration of β-aminopropionitrile (BAPN). The ability of migration was assessed by wound-healing assay. The ability of adhesion was detected by homogenous and heterogeneous adhesion experiments.

RESULTSCompared that with 0 mmol/L BAPN, the ability of migration of the cells after treatment with 0.2 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was increased from (6.97 ± 0.07) × 10(3)/ml to (7.78 ± 0.11) × 10(3)/ml; and the number of cells with heterogeneous adhesion was decreased from (8.98 ± 0.15) × 10(3)/ml to (8.35 ± 0.10) × 10(3)/ml, both < 0.05. Compared with that of cells treated with 0 mmol/L and 0.2 mmol/L BAPN, the migration ability of cells after treatment with 0.3 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was raised to (8.02 ± 0.11) × 10(3)/ml and the number of cells with heterogeneous adhesion was down to (7.93 ± 0.07) × 10(3)/ml (P < 0.05).

CONCLUSIONLOX may promote the metastasis of cancer cells by enhancing invasion, increasing heterogeneous adhesion and decreasing homogeneous adhesion.

Aminopropionitrile ; administration & dosage ; pharmacology ; Cell Adhesion ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Neoplasm Invasiveness ; Protein-Lysine 6-Oxidase ; antagonists & inhibitors ; metabolism ; physiology ; Stomach Neoplasms ; enzymology ; pathology

OBJECTIVETo evaluate the reliability and application of GeneSearch(TM) breast lymph node assay (Genesearch), a real-time fluorescence quatitative PCR method, in intraoperative assay of metastasis in sentinel lymph nodes (SLNs) from breast cancer patients.

METHODSTotally 140 SLNs from 80 patients with breast carcinoma were prospectively studied from May 2010 to August 2010. The 80 patients included 78 women and 2 men who ranged in age from 29 to 85 years, and the median age is 49 years. The expression of CK19 and mammaglobulin in all 140 SLNs were detected by Genesearch, and the results were compared with that of histological evaluation of both frozen and paraffin-embedded sections.

RESULTSAmong SLNs, by histological analyses, there were 121 without metastasis, 17 with macrometastasis, 2 with micrometastasis, and none of isolated tumor cell. By Genesearch, there were 119 without metastasis and 21 with metastasis. Genesearch showed sensitivity of 89.4%, positive predictive value of 81.0%, negative predictive value of 98.3% and specificity of 96.7% by comparing to histological analyses. The concordance between Genesearch and histological analysis was 95.7%. The sensitivity of Genesearch was 15/17 for macrometastasis and 2/2 for micrometastasis.

CONCLUSIONSGenesearch detection presents high sensitivity and specificity in evaluating metastasis of sentinel lymph nodes in breast cancer, but strict performance technically is necessary to avoid false positive and false negative results. Inability of further subtyping for the positive cases might be the key limitations for wide application of this method.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; surgery ; Breast Neoplasms, Male ; pathology ; surgery ; Female ; Humans ; Intraoperative Period ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; Male ; Middle Aged ; Neoplasm Micrometastasis ; diagnosis ; Predictive Value of Tests ; Sensitivity and Specificity ; Sentinel Lymph Node Biopsy

OBJECTIVETo explore the effect of cardiopulmonary bypass (CPB) on the profile of protein expression in peripheral blood mononuclear cells (PBMCs).

METHODSEleven patients undergoing cardiac surgery under cardiopulmonary bypass were enrolled in the study. Peripheral blood samples were collected before CPB (T0), 1 h after CPB (T1) and at the end of operation (T2), and PBMCs were obtained by gradient centrifugation. The profile of protein expression was analyzed using 2-D gel electrophoresis (2-DE) and mass spectrometry. The candidate proteins were further identified by Western blotting.

RESULTCompared to protein profile at T0, 12 protein spots were identified to be up-regulated in PBMCs at T1 (P <0.05), among which S100A9 reached the peak level at T1 and decreased after operation,but not returned to its initial level.

CONCLUSIONResults indicate that 12 proteins are likely to be involved in CPB, however, their roles need to be elucidated.

Adult ; Cardiopulmonary Bypass ; Electrophoresis, Gel, Two-Dimensional ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism ; Proteomics ; Young Adult

OBJECTIVETo study the etiological agent of hand-foot-and-mouth disease (HFMD), and to genetically characterize enterovirus 71 (EV71) isolated from clinical specimens of HFMD patients in Nanjing in 2010.

METHODThroat swab specimens were collected from 248 inpatients with HFMD in Nanjing Children's Hospital and then viral isolation was performed. Real-time PCR was used for detection of EV71, coxsackievirus A16 (Cox A16) and other enteroviruses from the positive isolates. Twenty EV71 strains from different clinical types of cases were selected for entire VP1 coding gene amplification and sequencing, finally a phylogenetic tree was constructed among the 20 EV71 strains and EV71 representative strains of known genotypes and subgenotypes.

RESULTFrom the 248 throat swabs specimens, 110 EV71 strains, 28 Cox A16 strains, and 8 other enterovirus strains were isolated and the positive rate was 44.35%, 11.29%, 3.23%, respectively. Then nucleotide sequencing was performed on the 20 EV71 strains. There was little difference in the nucleotide and the amino acid sequences among the 20 EV71 strains, the homology was 95.51%-100% and 98.32%-100%, respectively. The phylogenetic tree showed that all the 20 EV71 strains belonged to C4 subgenotype.

CONCLUSIONEV71 was the main pathogen of HFMD in Nanjing in 2010 and all the analyzed isolates belonged to C4 serotype. No significant difference was found in sequence of VP1 region of EV71 isolated from different clinical types of cases.

Amino Acid Sequence ; Capsid Proteins ; genetics ; Child ; Child, Preschool ; China ; epidemiology ; Enterovirus A, Human ; genetics ; isolation & purification ; Female ; Genotype ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Male

Objective:To assess the concordance between different anthropometric indexes in the Global Leaders Initiated Malnutrition Standards(GLIM)and the Geriatric Risk Index(GNRI)for assessing muscle mass,and to explore performance-based criteria for GLIM muscle content appropriate for elderly patients with intermediate and advanced tumors.Methods:312 patients admitted to Shanghai Tenth People's Hospital from September 2022 to June 2023 were included.All patients were assessed nutritionally using the GLIM,applying the three methods of grip strength,upper arm circumference,and calf circumference as expressive criteria for assessing muscle content,and the diagnostic value of the three tools corresponding to the GLIM criteria was assessed using the GNRI as a reference standard.Results:Among 312 elderly patients with intermediate to advanced tumors,127(40.71％)and 138(44.23％),128(41.03％)and 162(51.92％)were diagnosed as malnourished based on the GNRI and GLIM---grip strength,GLIM---calf circumference,and GLIM---upper arm circumference in nutritional assessment,respectively.The GNRI and GLIM--Grip strength were both associated with incidence of complications and length of hospital stays.Using GNRI as a reference standard,GLIM-grip strength diagnosed malnutrition with good consistency(K value=0.692,P＜0.001),followed by calf circumference(K value=0.688,P＜0.001);compared with the other two indexes,the AUC of GLIM-grip strength was 0.851,with the correctness was 84.3％,with the best diagnostic value.Conclusion:Grip strength can be used as a practical and convenient muscle content performance-based criterion in the GLIM standards and is expected to be promoted in the diagnosis of malnutrition in elderly patients with intermediate and advanced malignancies.

Adult ; Antifungal Agents ; therapeutic use ; Eye Infections, Fungal ; diagnosis ; drug therapy ; Humans ; Keratitis ; diagnosis ; drug therapy ; Male