Background Bevacizumab is primarily aimed at pathologic angiogenesis for off-label uses such as the treatment of ocular neovascular disorders.However,as a new anti-fibrotic and anti-angiogenic agent following trabeculectomy,the safety and efficacy of bevacizumab by multiple-time and high-dose subconjunctival injection are still under study.Objective This study was to assess the safety and efficacy of bevacizumab after multiple-time and high-dose subconjunctival injections.Methods Regular trabeculectomy filtration surgery was performed on both eyes of 18 clean New Zealand White rabbits 0.1ml of bevacizumab(25g/L) was subconjunctivally injected intraoperatively and 3,5,7 days postoperatively in the left eyes of rabbits,and no any intervene in the right eyes were as normal controls.Bleb morphology was examined every 2 days and graded based on Moorefield's criteria and compared between the bevacizumab-treated eyes and normal saline(NS) eyes.The animals were sacrificed at 10,20 and 30 days after surgery respectively.The histopathological changes of the blebs were detected by hematoxylin and eosin stain to evaluate the cellular element around the bleb,and Masson stain was used to assess the degree of fibroblast proliferation.The degree of vascularity of bleb was identified by anti-vWf stain.Approval of this protocol was obtained and permitted from People's Hospital Institutional Animal Care and Use Committee of Peking University.The use of experimental animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results Compared to the NS-treated eyes,bevacizumab-treated eyes showed the larger and more diffusely elevated blebs with the significant difference(2.48±0.22cm2 versus 1.73±0.27cm2,t=5.194,P＜0.05).The survival time of the filtration bleb in bevacizumab panel was longer in bevacizumab-treated eyes compared to control eyes,showing a significantly difference between them(21.0±1.56 days versus 12.5±1.97 days,t=3.830,P=0.005).Histological and immunohistochemical analysis confirmed that bleb and adjacent conjunctiva vascularity(A value) was significantly less in bevacizumab-treated eyes than that in control eyes at 20 days after surgery with the difference value 14320.7±4134.9(t=12.275,P＜0.05),and fibroblast deposition value was evidently diminished after bevacizumab treatment at 30 days following surgery in comparison with control eyes with the mean difference 0.27±0.03(t=15.980,P＜0.05＝.Conclusion Repeated subconjunctival injection of bevacizumab can effectively prolong the survival time of bleb in a rabbit model of trabeculectomy and limit the degree and area of vascularization in 30 days following surgery.Bevacizumab inhibit fibroblast-meditated tissue formation significantly in the later phase of vascularization after trabeculectomy.

OBJECTIVE: To observe the expression of aquaporin 4 (AQP4) in diffuse brain injury (DBI) of rats and to explore the corresponding effect of AQP4 for brain edema. METHODS: The rat model of DBI was established using Marmarou's impact-compression trauma model. Brain water content was measured by dry-wet weight method. Blood-brain barrier permeability was evaluated by Evans blue (EB) staining. Immunohistochemical method was used to observe the expression of AQP4. RESULTS: Brain water content increased after 3 h and peaked at 24 h after DBI. Brain EB content significantly increased and peaked at 12 h after DBI. The expression of AQP4 significantly increased after 3 h and peaked at 24 h after DBI, and the number of AQP4 positive astrocytes increased. CONCLUSION The increment of the permeability of blood-brain barrier and the expression of AQP4 may contribute to the development of brain edema in rat DBI. The change of AQP4 expression in astrocytes may also contribute to determine DBI.
Animals ; Aquaporin 4/metabolism* ; Astrocytes ; Blood-Brain Barrier/metabolism* ; Brain ; Brain Edema/metabolism* ; Brain Injuries/metabolism* ; Cell Membrane Permeability/genetics* ; Disease Models, Animal ; Permeability ; Rats ; Water

OBJECTIVETo establish a disease-syndrome conjugated animal model, the mini-swine coronary heart disease (CHD) model of phlegm-stasis cementation syndrome type, by high fat diet feeding and coronary artery balloon injury.

METHODSMini-swine were randomly divided into the control group and the model group, 6 in each group. They were fed with common forage and high fat forage respectively for 10 weeks and the coronary left anterior descending branch in the model group was injured by balloon intervention technique after 2-week feeding to establish CHD model. The model establishment and its physiopathological indices were evaluated by examinations on body mass index (BMI), blood levels of lipid, high-sensitivity C-reactive protein (hs-CRP), body surface electrocardiograph (BS-ECG), coronary angiography and pathological indices.

RESULTSBMI, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), hs-CRP, sigma-ST and N-ST indicated by BS-ECG in the model group were all higher than those in the control group respectively (P < 0.05 or P < 0.01). Coronary angiography showed coronary lumen narrowed with apparent lumen loss, showing a significant difference as compared with the control group (P < 0.01). In EVG staining, the diameters of lumen in the model group was obviously narrow with intima proliferation, also significantly different to those in the control group (P < 0.01).

CONCLUSIONDisease-syndrome combined model for coronary heart disease of phlegm-stasis cementation syndrome type in mini-swine could be established by high fat diet feeding with coronary arterial injury.

Animals ; Coronary Disease ; etiology ; Diagnosis, Differential ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Female ; Male ; Medicine, Chinese Traditional ; methods ; Random Allocation ; Swine ; Swine, Miniature ; Syndrome

Along with the rapid development of molecular biology, cell biology, genetics, and immunology, there is a new understanding on the pathogenesis of pituitary adenomas. The pathogenesis of pituitary adenomas is considered to be related with gene mutation, growth factors, cell receptors, transcription factors, and cellular signaling pathways.
Adenoma ; genetics ; metabolism ; Humans ; Mutation ; Pituitary Neoplasms ; genetics ; metabolism ; Signal Transduction

Objective To evaluate the clinical and radiographic characteristics and function of erosive hand osteoarthritis (EOA) patients. Methods Data were obtained from 19 patients with EOA, including their social conditions, clinical conditions, radiographic scores and hand function evaluation. The number of hand osteoarthritis (HOA) patients was 312. The control group consisted of non-EOA patients with hand osteoarthritis with a ratio of 4:1 to EOA patients. A non-parameter test analysis was performed. All data were analyzed by SPSS 23.0 statistical analysis, t test, χ2 test, Fisher exact probility and Spearman's correlations analysis were used for statistical analysis. Results Totally data of 19 patients were collected. Eighteen were female. Onset age was (56±8). Average duration was 56 (12~120) months. FIHOA scores of all the EOA patients were at least 5. All the erosions of 39 joints were characteristically central and erosive changes in 7 joints (18%) showed up as gull-wing. Among 39 erosive joints, including 12 (31%) E and 27 (69%) R, 34 (87%) distal interphalangeal joints were involved. Data analysis found out that EOA patients had longer disease duration (Z=2.610, P=0.009), more severe K-L level (44 ±11 vs 26 ±7, t=7.134, P<0.01), higher AUSCAN total score (28±6 vs 21±7, t=3.781, P<0.01) and higher AUSCAN function score (18±6 vs 12±6, t=4.042, P<0.01). The differences of ESR and CRP were not significant between EOA and non-EOA patients. Conclusion Erosions seen in EOA patients are centrally located gull-wing in the DIP joints. EOA patients have longer duration, more severe radiographic damage and worse joint function.

Aviation ; Humans ; Physical Fitness ; Resistance Training ; Schools ; Students

Adolescent ; Adult ; Female ; Humans ; Leg Bones ; abnormalities ; surgery ; Male ; Middle Aged ; Soft Tissue Injuries ; surgery ; Surgical Flaps

On the base of reviewing the current literatures concerning the animal models with syndromes of Chinese medicine and investigating thee present state of the syndrome models, the authors have put forward a definition that research of animal models with the syndromes of Chinese medicine should be combined with clinical methods, and commented the potential application. Further it was suggested that clinical methods should be used in the exploration of scientific principles and the progresses on syndromes of Chinese medicine. In addition, intervene and evaluation of Chinese herbal medicine in animal model with integrated diseases and syndromes should be emphasized to establish a platform with special properties of TCM.
Animals ; Disease Models, Animal ; Medicine, Chinese Traditional ; methods ; Syndrome

OBJECTIVEGap junctions, the clusters of intercellular channels, play an important role in synchronizing electrical activity. This study investigated the effect of gap junction blocker carbenoxolone (CBX) on epileptic activity in pentylenetetrazo (PTZ)-kindled rats.

METHODSThirty adult male SD rats were randomly divided into three groups: control, PTZ-kindled and CBX-treated groups (n=10 each). The rats from the PTZ-kindled and the CBX-treated groups were intraperitoneally injected with PTZ (35 mg/kg x d) to induce epilepsy. After epilepsy kindling, they were intraperitoneally injected for 3 days with CBX (10 mg/kg) (CBX-treated group) or with normal saline (PTZ-kindled group). The control group received intraperitoneal injections of normal saline. Anti-GFAP, anti-Fos, and anti-NMDARZ immunohistochemical ABC methods were used to detect the expression of GFAP-Li, Fos-Li and NMDAR2-Li in the hippocampus respectively.

RESULTSSpontaneous seizures occurred in PTZ-kindled epileptic rats. CBX administration reduced spontaneous seizures. The NMDAR2-Li and Fos-Li neurons as well as GFAP-Li astrocytes in hippocampi increased in PTZ-kindled epileptic rats compared with controls. The numbers of Fos-Li (93.75 +/-7.94 vs 165.25 +/-15.87, P < 0.05) and NMDAR2-Li neurons (61.47 +/-3.62 vs 148.72 +/-14.53, P < 0.01) in the CBX-treated group were significantly less than in the PTZ-kindled group. There were no significant differences in the GFAP-Li expression between the CBX-treated and the PTZ-kindled groups.

CONCLUSIONSCBX may inhibit spontaneous seizures and decrease the numbers of Fos-Li and NMDARZ-Li neurons, thus providing anti-epileptic effects.

Animals ; Carbenoxolone ; pharmacology ; Epilepsy ; drug therapy ; metabolism ; Gap Junctions ; drug effects ; Glial Fibrillary Acidic Protein ; analysis ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Kindling, Neurologic ; drug effects ; metabolism ; Male ; Pentylenetetrazole ; Proto-Oncogene Proteins c-fos ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; analysis

OBJECTIVETo investigate the association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).

METHODSThis study involved 121 patients with T2DM and 94 with diabetic macroangiopathy. The polymorphisms of G8790A in ACE2 gene was analyzed using PCR-restriction fragment length polymorphism analysis in these patients, and the clinical, biochemical and echocardiographic data were also analyzed.

RESULTSNo obvious difference was found in the genotyping data between the two groups. Among the male patients with diabetic macroangiopathy, the interventricular septal end-diastolic thickness (IVSTd) were significantly greater in patients of GG genotypes of ACE2 gene G8790A than in those of AA genotypes (P<0.01), and the left ventricular mass (LVMI) and urine protein were also significantly higher in GG genotypes (P<0.05). No similar results were found the uncomplicated diabetic group or the female diabetic patients with CAD.

CONCLUSIONThe ACE2 gene G8790A polymorphism plays a role in the pathogenesis of CAD in patients with type 2 diabetes, suggesting that ACE2 genotyping is helpful to screen the susceptible patients.

Adult ; Aged ; Alleles ; Base Sequence ; Case-Control Studies ; Coronary Disease ; complications ; genetics ; Diabetes Mellitus, Type 2 ; complications ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Sequence Analysis, DNA