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

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

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

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.

Objective To evaluate the clinical efficacy and safety of capecitabine combined with oxaliplatin in the treatment of advanced esophago-gastric junction adenocarcinoma.Methods Eighty patients with advanced esophago -gastric junction adenocarcinoma were random-ly divided into control group ( n=40 ) and treatment group ( n=40 ).Control group was treated with 75 mg· m-2 docetaxel, intravenous infu-sion, day 1 +20 mg· m-2 cisplatin , intravenous infusion, day 1 +750 mg· m-2 5-fluorouracil, continuous infusion for 120 h, from day 1.Treatment group was received 120 mg · m-2 oxaliplatin , intravenous infusion , qd ( after 2 weeks treatment , discontinuation 1 week ) +7.5 mg · kg -1 recombinant human endostatin , intravenous infusion , qd +2000 mg· m-2 capecitabine, oral, bid(after 2 weeks treatment, discon-tinuation 1 week).Two groups were received 3 courses of treatment , 21 d for a course.The clinical efficacy , levels of tumor specific macromole-cular glycoprotein antigen 19 -9 ( CA199 ) , cancer embryo antigen (CEA), vascular endothelial growth factor (VEGF) and cell transmembrane notch ligand 4 (DLL4), and the inci-dence of adverse drug reactions were compared between two groups.Results After treatment, the total effective rate in treatment group was significantly higher than that in control group ( 90.00% vs 72.50%, P<0.05 ).The levels of CA199, CEA, VEGF, DLL4 after treatment in two groups were significantly lower than those before treatment ( P<0.05 ) , and after treatment , these indexes in treatment group were lower than those in control group with signifi-cant difference ( P<0.05 ).The incidence of adverse drug reactions in treatment was lower than that in control group with significant difference ( 15.00% vs 32.50%, P<0.05 ).Conclusion Capecitabine combined with oxaliplatin have a definitive clinical efficacy and safety for the treatment of advanced esophago -gastric junction adenocarcinoma , which can significantly reduce the levels of CA 199, CEA, VEGF and DLL4.

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

Tetramethylpyrazine (TMP), an effective component of traditional Chinese medicine Chuanxiong, is commonly used to resolve embolism. Its possible therapeutic effect against atherosclerosis has received considerable attention recently. Angiotensin II (Ang II) is highly implicated in the proliferation of vascular smooth muscle cells (VSMCs), resulting in atherosclerosis. The mechanisms of TMP in the proliferation of VSMCs induced by Ang II remain to be defined. The present study was aimed to study the effect of TMP on Ang II-induced VSMC proliferation through detection of nuclear factor-kappaB (NF-kappaB) activity and bone morphogenetic protein-2 (BMP-2) expression. Primary cultured rat aortic smooth muscle cells were divided into the control group, Ang II group, Ang II + TMP group and TMP group. Cells in each group were harvested at different time points (15, 30 and 60 min for detection of NF-kappaB activity; 6, 12 and 24 h for measurement of BMP-2 expression). NF-kappaB activation was identified as nuclear staining by immunohistochemistry. BMP-2 expression was observed through Western blot, immunohistochemistry and in situ hybridization. The results showed that: (1) Ang II stimulated the activation of NF-kappaB. Translocation of NF-kappaB p65 subunit from cytoplasm to nucleus appeared as early as 15 min, peaked at 30 min (P<0.01) and declined after 1 h. (2) TMP inhibited Ang II-induced NF-kappaB activation (P<0.01). (3) Ang II increased BMP-2 expression at 6 h but declined it significantly at 12 and 24 h (P<0.01). (4) BMP-2 expression was also kept at high level at 6 h in Ang II + TMP group but maintained at the normal level at 12 and 24 h. (5) There was no significant difference in NF-kappaB activation and BMP-2 expression between the control group and TMP group. These results indicate that TMP inhibits Ang II-induced VSMC proliferation through repression of NF-kappaB activation and BMP-2 reduction, and BMP-2 expression is independent of the NF-kappaB pathway. In conclusion, TMP has therapeutic potential for the treatment of atherosclerosis.
Angiotensin II ; antagonists & inhibitors ; Animals ; Atherosclerosis ; drug therapy ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; analysis ; antagonists & inhibitors ; Immunohistochemistry ; Muscle, Smooth, Vascular ; cytology ; drug effects ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; NF-kappa B ; analysis ; antagonists & inhibitors ; Pyrazines ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; analysis ; antagonists & inhibitors

OBJECTIVETo investigate the potential genetic mode of aggressive periodontitis (AgP) in Chinese Han nationality.

METHODSA total of 233 subjects from 73 nuclear families were recruited. All probands were diagnosed according to the criteria of AgP in 1999 classification of periodontal diseases. Ninety parents, 35 siblings and three grandparents and two offspring were examined based on full-mouth periodontal chartings (including parameter of probing depths, attachment loss, bleeding on probing at six sites per tooth) and full-mouth periapical radiographs. The genetic ratio was calculated and analyzed by the methods of Edwards and simple segregation.

RESULTSThe prevalence of AgP in probands' siblings was close to the square root of the prevalence of general population. The segregation ratio was 0.2419, which was close to the theoretical ratio for autosomal recessive inheritance. However, autosomal dominant inheritance could not be rejected in families whose parent(s) suffered from severe chronic periodontitis.

CONCLUSIONSThe genetic heterogeneity of AgP existed in Chinese Han nationality. The genetic mode was autosomal recessive inheritance in general, and autosomal dominant inheritance could not be excluded in families whose parent(s) suffered from severe chronical periodontitis. The results imply the genetic heterogeneity of AgP, and further demonstrate that AgP was a multifactorial disease with major genetic component in the disease etiology.

Aggressive Periodontitis ; epidemiology ; genetics ; Asian Continental Ancestry Group ; genetics ; Chronic Periodontitis ; epidemiology ; genetics ; Female ; Genes, Dominant ; Genes, Recessive ; Genetic Heterogeneity ; Humans ; Male ; Pedigree ; Prevalence ; Surveys and Questionnaires