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1.
Science ; 383(6686): 1014-1019, 2024 Mar.
Article En | MEDLINE | ID: mdl-38422145

The imine-exchange strategy makes single-crystal growth of covalent organic frameworks (COFs) with large size (>15 microns) possible but is a time-consuming process (15 to 80 days) that has had limited success (six examples) and restricts structural characterization to synchrotron-radiation sources for x-ray diffraction studies. We developed a CF3COOH/CF3CH2NH2 protocol to harvest single-crystal COFs within 1 to 2 days with crystal sizes of up to 150 microns. The generality was exemplified by the feasible growth of 16 high-quality single-crystal COFs that were structurally determined by laboratory single-crystal x-ray diffraction with resolutions of up to 0.79 angstroms. The structures obtained included uncommon interpenetration of networks, and the details of the structural evolution of conformational isomers and host-guest interaction could be determined at the atomic level.

2.
Fa Yi Xue Za Zhi ; 39(4): 382-387, 2023 Aug 25.
Article En, Zh | MEDLINE | ID: mdl-37859477

OBJECTIVES: To study the virtual reality-pattern visual evoked potential (VR-PVEP) P100 waveform characteristics of monocular visual impairment with different impaired degrees under simultaneous binocular perception and monocular stimulations. METHODS: A total of 55 young volunteers with normal vision (using decimal recording method, far vision ≥0.8 and near vision ≥0.5) were selected to simulate three groups of monocular refractive visual impairment by interpolation method. The sum of near and far vision ≤0.2 was Group A, the severe visual impairment group; the sum of near and far vision <0.8 was Group B, the moderate visual impairment group; and the sum of near and far vision ≥0.8 was Group C, the mild visual impairment group. The volunteers' binocular normal visions were set as the control group. The VR-PVEP P100 peak times measured by simultaneous binocular perception and monocular stimulation were compared at four spatial frequencies 16×16, 24×24, 32×32 and 64×64. RESULTS: In Group A, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 24×24, 32×32 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group B, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 16×16, 24×24 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group C, there was no significant difference between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at all spatial frequencies (P>0.05). There was no significant difference in the P100 peak times measured at all spatial frequencies between simulant visual impairment eyes and simultaneous binocular perception in the control group (P>0.05). CONCLUSIONS: VR-PVEP can be used for visual acuity evaluation of patients with severe and moderate monocular visual impairment, which can reflect the visual impairment degree caused by ametropia. VR-PVEP has application value in the objective evaluation of visual function and forensic clinical identification.


Evoked Potentials, Visual , Virtual Reality , Humans , Vision, Ocular , Vision, Binocular/physiology , Vision Disorders/diagnosis
3.
Int J Ophthalmol ; 16(7): 1005-1014, 2023.
Article En | MEDLINE | ID: mdl-37465511

AIM: To predict best-corrected visual acuity (BCVA) by machine learning in patients with ocular trauma who were treated for at least 6mo. METHODS: The internal dataset consisted of 850 patients with 1589 eyes and an average age of 44.29y. The initial visual acuity was 0.99 logMAR. The test dataset consisted of 60 patients with 100 eyes collected while the model was optimized. Four different machine-learning algorithms (Extreme Gradient Boosting, support vector regression, Bayesian ridge, and random forest regressor) were used to predict BCVA, and four algorithms (Extreme Gradient Boosting, support vector machine, logistic regression, and random forest classifier) were used to classify BCVA in patients with ocular trauma after treatment for 6mo or longer. Clinical features were obtained from outpatient records, and ocular parameters were extracted from optical coherence tomography images and fundus photographs. These features were put into different machine-learning models, and the obtained predicted values were compared with the actual BCVA values. The best-performing model and the best variable selected were further evaluated in the test dataset. RESULTS: There was a significant correlation between the predicted and actual values [all Pearson correlation coefficient (PCC)>0.6]. Considering only the data from the traumatic group (group A) into account, the lowest mean absolute error (MAE) and root mean square error (RMSE) were 0.30 and 0.40 logMAR, respectively. In the traumatic and healthy groups (group B), the lowest MAE and RMSE were 0.20 and 0.33 logMAR, respectively. The sensitivity was always higher than the specificity in group A, in contrast to the results in group B. The classification accuracy and precision were above 0.80 in both groups. The MAE, RMSE, and PCC of the test dataset were 0.20, 0.29, and 0.96, respectively. The sensitivity, precision, specificity, and accuracy of the test dataset were 0.83, 0.92, 0.95, and 0.90, respectively. CONCLUSION: Predicting BCVA using machine-learning models in patients with treated ocular trauma is accurate and helpful in the identification of visual dysfunction.

4.
J Clin Transl Hepatol ; 11(1): 110-117, 2023 Feb 28.
Article En | MEDLINE | ID: mdl-36406330

Background and Aims: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide. The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients. Integrin α6 is a promising cell surface target for molecular imaging of HCC, where it is overexpressed and is a prognostic biomarker. We previously identified an integrin α6-targeted peptide CRWYDENAC (RWY) that has been used for positron emission tomography (PET) imaging of HCC in mouse models. Methods: We labeled the integrin α6-targeted RWY peptide with cyanine 7 (Cy7) to form an optical probe (Cy7-RWY) for near infrared fluorescent (NIRF) and photoacoustic (PA) imaging in HCC. Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrin α6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control. NIRF and PA images of mice were collected from 0 to 48 h after injection. Results: Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h. Conclusions: Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice, and has potential clinical application for HCC detection.

5.
World J Clin Cases ; 8(16): 3458-3464, 2020 Aug 26.
Article En | MEDLINE | ID: mdl-32913852

BACKGROUND: The incidence and prevalence of atrial fibrillation are increasing each year, and this condition is one of the most common clinical arrhythmias. AIM: To investigate the levels and significance of serum fibroblast growth factor 23 (FGF-23) and miR-208b in patients with atrial fibrillation and their relationship with prognosis. METHODS: From May 2018 to October 2019, 240 patients with atrial fibrillation were selected as an observation group, including 134 with paroxysmal atrial fibrillation and 106 with persistent atrial fibrillation; 150 patients with healthy sinus rhythm were selected as a control group. The serum levels of FGF-23 and miR-208b in the two groups were measured. In the observation group, cardiac parameters were determined by echocardiography. RESULTS: The serum levels of FGF-23 and miR-208b in the observation group were 210.20 ± 89.60 ng/mL and 5.30 ± 1.22 ng/mL, which were significantly higher than the corresponding values in the control group (P < 0.05). In the observation group, the serum levels of FGF-23 and miR-208b in patients with persistent atrial fibrillation were 234.22 ± 70.05 ng/mL and 5.83 ± 1.00 ng/mL, which were significantly higher than the corresponding values in patients with paroxysmal atrial fibrillation (P < 0.05). The left atrial dimension (LAD) of patients with persistent atrial fibrillation was 38.81 ± 5.11 mm, which was significantly higher than that of patients with paroxysmal atrial fibrillation (P > 0.05). The serum levels of FGF-23 and miR-208b were positively correlated with the LAD (r = 0.411 and 0.382, P < 0.05). In the observation group, the serum levels of FGF-23 and miR-208b in patients with a major cardiovascular event (MACE) were 243.30 ± 72.29 ng/mL and 6.12 ± 1.12 ng/mL, which were significantly higher than the corresponding values in patients without a MACE (P < 0.05). CONCLUSION: The serum levels of FGF-23 and miR-208b are increased in patients with atrial fibrillation and are related to the type of disease, cardiac parameters, and prognosis.

6.
ChemistryOpen ; 7(4): 288-296, 2018 04.
Article En | MEDLINE | ID: mdl-29657915

Contrast enhancement agents are often employed in magnetic resonance imaging (MRI) for clinical diagnosis and biomedical research. However, the current theory on MRI contrast generation does not consider the ubiquitous presence of macromolecular crowders in biological systems, which poses the risk of inaccurate data interpretation and misdiagnosis. To address this issue, herein the macromolecular crowding effects on MRI contrast agent are investigated with the 1H relaxation rate of water in aqueous solutions of Dotarem with different concentrations of macromolecules. Two representative macromolecular crowder systems are used: polyethylene glycol (with no specific secondary structure) and bovine serum albumin (with compact secondary and tertiary structures). The water 1H relaxation rates in various solutions are measured in a fixed magnetic field and in variable magnetic fields. The results show significant crowding effects for both crowders. The relaxation rate is proportional to the concentration of the MRI contrast agent but shows conspicuous superlinearity with respect to the concentration of the crowder. The size of polyethylene glycol does not affect the relaxivity of water in Dotarem solutions. The above effects are verified with T1- and T2-weighted NMR microimages. These results highlight the importance of the effect of macromolecular crowding on the MRI contrast agent and are valuable for understanding the mechanism of MRI contrast agents and designing new-generation MRI contrast agents.

7.
J Gastrointestin Liver Dis ; 27(1): 73-81, 2018 03.
Article En | MEDLINE | ID: mdl-29557418

BACKGROUND AND AIMS: Growing evidence has shown that M2-PK is involved in cancer diagnosis and prognosis. The overall diagnostic accuracy of the pyruvate kinase isoenzyme type M2 (M2-PK) in biliary tract carcinoma (BTC) remains controversial. We performed a meta-analysis to evaluate the diagnostic value of M2-PK for BTC. METHODS: The online PubMed, Cochrane, Web of Science, and Embase databases were searched for eligible studies published until August 8th, 2017. The Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate study quality. All statistical analyses were conducted with Stata 12.0. RESULTS: We included 7 studies from 5 articles with 410 patients with BTC and 438 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for M2-PK in the diagnosis of BTC were 0.79 (95%CI 0.70-0.86), 0.81 (95%CI 0.71-0.88), 4.1 (95%CI 2.5-6.8), 0.26 (95%CI 0.16-0.41), 17.159 (95%CI 5.468-54.071), and 0.87 (95%CI 0.83-0.89), respectively. The same indicators assessed for CA19-9 were as follows: 0.70 (95%CI 0.62-0.77), 0.71 (95%CI 0.45-0.87), 2.38 (95%CI 1.2-4.73), 0.43 (95%CI 0.34-0.53), 6.28 (95%CI 2.4-16.44) and 0.73 (95%CI 0.69-0.77), respectively. Additionally, the diagnostic value of M2-PK varied based on characteristics of golden methods and different cut-off values. CONCLUSIONS: This meta-analysis showed that M2-PK had a better diagnostic accuracy for BTC compared with CA19-9, with moderate diagnostic performance. However, prospective studies are required to confirm its diagnostic value.


Bile/metabolism , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/metabolism , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/metabolism , Pyruvate Kinase/blood , Biomarkers, Tumor/metabolism , CA-19-9 Antigen/blood , Humans , Pyruvate Kinase/metabolism
8.
Med Sci Law ; 58(1): 58-61, 2018 Jan.
Article En | MEDLINE | ID: mdl-29363384

Dental injuries, especially of the incisors, caused by punches in violent criminal attacks could be seen in daily forensic casework involving the identification of injuries to a living body. Sometimes, when there is neither circumstantial evidence nor information about the surrounding circumstances, it is difficult to discern the cause of these injuries and the manner in which they were inflicted. As an example of clinical forensic medicine, we present the case of a 58-year-old woman whose teeth were injured when fighting with her son-in-law over household affairs with no witnesses present. The two parties had conflicting stories about the cause of the woman's injury. The woman claimed that her teeth were lost while she was being beaten by her son-in-law, and the man argued that the damage to his mother-in-law's teeth was self-inflicted when she bit his fingers. The police attending the crime called for a forensic examination. Forensic practitioners analysed the mechanism of the tooth loss using multi-slice spiral computed tomography (MSCT) and imaging reconstruction technology. Local alveolar bone (medial alveolar) fracture and a small area of alveolar bone loss were found on MSCT. Thus, forensic medical experts speculated that the woman's lower central and lateral incisors were lost as a result of a violent attack and were not self-inflicted. Finally, forensic practitioners helped police in avoiding a miscarriage of justice and wrongful conviction.


Alveolar Bone Loss/diagnostic imaging , Alveolar Process/diagnostic imaging , Alveolar Process/injuries , Jaw Fractures/diagnostic imaging , Physical Abuse , Alveolar Bone Loss/etiology , Female , Forensic Medicine , Humans , Jaw Fractures/etiology , Middle Aged , Tomography, Spiral Computed
9.
J Ophthalmol ; 2016: 4087096, 2016.
Article En | MEDLINE | ID: mdl-27688906

UNLABELLED: Objective. To explore the potential effects of methanol and its metabolite, formic acid, on rat retina function. Methods. Sprague-Dawley rats were divided into 3- and 7-day groups and a control. Experimental groups were given methanol and the control group were provided saline by gavage. Retinal function of each group was assessed by electroretinogram. Concentrations of methanol and formic acid were detected by GC/HS and HPLC, respectively. Results. The a and b amplitudes of methanol treated groups decreased and latent periods delayed in scotopic and photopic ERG recordings. The summed amplitudes of oscillatory potentials (OPs) of groups B and C decreased and the elapsed time delayed. The amplitudes of OS1, OS3, OS4, and OS5 of group B and OS3, OS4, and OS5 of group C decreased compared with the control group. The IPI1 of group B and IPI1-4 of group C were broader compared with the control group and the IPI1-4 and ET of group B were broader than group C. CONCLUSIONS: Both of scotopic and photopic retinal functions were impaired by methanol poisoning, and impairment was more serious in the 7-day than in the 3-day group. OPs, especially later OPs and IPI2, were more sensitive to methanol intoxication than other eletroretinogram subcomponents.

10.
Fa Yi Xue Za Zhi ; 31(1): 20-2, 27, 2015 Feb.
Article Zh | MEDLINE | ID: mdl-26058128

OBJECTIVE: To compare the correlation between contrast vision (LV) and sweep visual evoked potential acuity (SVEP-A) among people with emmetropia, mild myopia, and moderate myopia. METHODS: The CV and SVEP-A were tested individually in 96 eyes from healthy young volunteers, including 37 eyes of emmetropia, 27 eyes of mild myopia, and 32 eyes of moderate myopia. The statistic analysis was done by ANOVA analysis and rank sum test. RESULTS: (1) With the decrease of contrast, CV and SVEP-A decreased in every group. (2) At 100% contrast, the difference of CV between emmetropia and mild myopia had statistical significance (P<0.05). At 100%, 25% and 10% contrast, the difference of CV between emmetropia and moderate myopia had statistical significance (P<0.05). (3) In the same group, the difference of 100% and 25% contrast had statistical significance (P < 0.05). So was between 100% and 10% contrast. (4) At 100% and 10% contrast, the difference of CV and SVEP-A had statistical significance (P < 0.05). CONCLUSION: The CV of myopia relates to many factors including ametropia and fundus lesions. The correction of ametropia is important to the values of CV and SVEP-A.


Evoked Potentials, Visual/physiology , Myopia/physiopathology , Visual Acuity/physiology , Eye , Fundus Oculi , Humans , Neurologic Examination , Severity of Illness Index , Vision Tests/instrumentation
11.
Oncotarget ; 6(25): 21341-52, 2015 Aug 28.
Article En | MEDLINE | ID: mdl-26050198

ZD6474, a small molecule VEGFR and EGFR tyrosine kinase inhibitor, has been considered as a promising tumor-targeted drug in various malignancies. EGFR and cyclooxygenase-2 (COX-2) were found overexpressed in osteosarcoma in previous reports, so here we tried to explore the anti-osteosarcoma effect of ZD6474 alone or combination with celecoxib, a COX-2 inhibitor. The data demonstrated that ZD6474 inhibited the growth of osteosarcoma cells, and promoted G1-phase cell cycle arrest and apoptosis by inhibiting the activity of EGFR tyrosine kinase, and consequently suppressing its downstream PI3k/Akt and MAPK/ERK pathway. Additionally, daily administration of ZD6474 produced a dose-dependent inhibition of tumor growth in nude mice. Celecoxib also significantly inhibited the growth of osteosarcoma cells in dose-dependent manner, while combination of ZD6474 and celecoxib displayed a synergistic or additive antitumor effect on osteosarcoma in vitro and in vivo. The possible molecular mechanisms to address the synergism are likely that ZD6474 induces the down-regulation of COX-2 expression through inhibiting ERK phosphorylation, while celecoxib promotes ZD6474-directed inhibition of ERK phosphorylation. In conclusion, ZD6474 exerts direct anti-proliferative effects on osteosarcoma cells, and the synergistic antitumor effect of the combination of ZD6474 with celecoxib may indicate a new strategy of the combinative treatment of human osteosarcoma.


Bone Neoplasms/drug therapy , Celecoxib/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Osteosarcoma/drug therapy , Piperidines/pharmacology , Quinazolines/pharmacology , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Bone Neoplasms/metabolism , Celecoxib/administration & dosage , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/administration & dosage , Dose-Response Relationship, Drug , Down-Regulation , Drug Synergism , ErbB Receptors/metabolism , Female , G1 Phase , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Osteosarcoma/metabolism , Phosphorylation , Piperidines/administration & dosage , Quinazolines/administration & dosage , Xenograft Model Antitumor Assays
12.
Fa Yi Xue Za Zhi ; 31(6): 450-3, 2015 Dec.
Article Zh | MEDLINE | ID: mdl-27141803

OBJECTIVE: To investigate concentration and distribution in blood and tissues of formic acid after methanol intoxication in rats. METHODS: The Sprague-Dawley rats were divided into groups for control group and 3-day and 7-day intoxication treatment groups. The experimental groups were administered methanol by gavage with the initial dose of 8 mL/kg and followed with 4 mL/kg supplemental dose 24 h later. After 3 days and 7 days later, rats were killed by decapitation. Then samples of cardiac blood, liver, kidney, brain, heart and stomach of each group were collected. Formic acid concentrations were detected by high performance liquid chromatography. RESULTS: Formic acid concentrations in tissues were higher than in blood. Compared with 3-day intoxication group, there was an increase formic acid of concentration in brain and stomach in 7-day intoxication group, while a decrease in liver and kidney (P < 0.05). CONCLUSION: High performance liquid chromatography could be used to accurately detect formic acid. As the metabolite of methanol, formic acid accumulates in rat blood and tissues after intoxication and the concentrations in organs and tissues are obviously higher than in blood.


Formates/blood , Methanol/blood , Methanol/poisoning , Animals , Brain/metabolism , Chromatography, High Pressure Liquid , Kidney/metabolism , Liver/metabolism , Rats , Rats, Sprague-Dawley , Tissue Distribution
13.
Fa Yi Xue Za Zhi ; 30(4): 261-3, 2014 Aug.
Article Zh | MEDLINE | ID: mdl-25434087

OBJECTIVE: To compare the agreement of anterior chamber angle examination by ultrasound biomicroscope (UBM), slit lamp optical coherence tomography (SL-OCT), and gonioscopy in angle recession and angle closure. METHODS: The anterior chamber angle was measured with UBM, SL-OCT and gonioscopy in turns for temporal, nasal, superior and inferior quadrant in the same dark room. The results were compared with the agreement of the three methods in angle recession and angle closure by χ2 test and Kappa test. RESULTS: There were no statistically significant differences of the three methods in testing angle closure and angle recession (P>0.05). The consistency of UBM and gonioscopy was better (Kappa value of 0.882) than that of SL-OCT and gonioscopy (Kappa value of 0.624). CONCLUSION: When testing angle recession, UBM is better than SL-OCT with gonioscopy as the standard. When testing angle closure, UBM, SL-OCT and gonioscopy have good agreement.


Glaucoma, Angle-Closure , Gonioscopy , Microscopy, Acoustic , Tomography, Optical Coherence , Anterior Chamber , Humans , Intraocular Pressure , Slit Lamp
14.
Fa Yi Xue Za Zhi ; 30(3): 178-80, 2014 Jun.
Article Zh | MEDLINE | ID: mdl-25272870

OBJECTIVE: To study the characters of oscillatory potentials (OPs) of electroretinogram (ERG) after methanol intoxication in rats. METHOD: The SD rat models of methanol intoxication were established and divided into control group, 3-day intoxication group, 7-day intoxication group. The changes of OPs of ERG were recorded in a dark room. RESULTS: The total amplitudes of 3-day and 7-day intoxication groups decreased approximately 50% compared with that of the control group, while the schedule delayed approximately 16% and 61%, respectively. CONCLUSION: The characters of methanol intoxication in rats included delay in schedule and decline in the total amplitude of OPs.


Electroretinography , Methanol/poisoning , Retina/physiopathology , Animals , Rats
15.
Fa Yi Xue Za Zhi ; 30(6): 470-3, 2014 Dec.
Article Zh | MEDLINE | ID: mdl-25816583

alphaB-crystallin is the structural protein of vertebrate lens, which is widely expressed in non-lens tissue. As one of the heat shock protein family members, alphaB-crystallin possesses biological properties of molecular chaperones and anti-apoptotic effects. Multi-factor injuries, such as retinopathy, inflammation and nervous system diseases, have a closely relationship with alphaB-crystallin. This paper reviews the research progress of the expression and mechanism of alphaB-crystallin in retina and extraocular tissues and organs.


Gene Expression Regulation, Developmental , Heat-Shock Proteins/metabolism , alpha-Crystallin B Chain/metabolism , Crystallins , Humans , Lens, Crystalline , Retina
16.
Fa Yi Xue Za Zhi ; 29(4): 286-9, 294, 2013 Aug.
Article Zh | MEDLINE | ID: mdl-24350547

Multifocal visual electrophysiology, consisting of multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP), can objectively evaluate retina function and retina-cortical conduction pathway status by stimulating many local retinal regions and obtaining each local response simultaneously. Having many advantages such as short testing time and high sensitivity, it has been widely used in clinical ophthalmology, especially in the diagnosis of retinal disease and glaucoma. It is a new objective technique in clinical forensic medicine involving visual function evaluation of ocular trauma in particular. This article summarizes the way of stimulation, the position of electrodes, the way of analysis, the visual function evaluation of mfERG and mfVEP, and discussed the value of multifocal visual electrophysiology in forensic medicine.


Electroretinography/methods , Evoked Potentials, Visual/physiology , Eye Injuries/diagnosis , Retina/physiology , Vision, Ocular/physiology , Electrodes , Electrophysiology , Eye Injuries/physiopathology , Forensic Medicine/methods , Glaucoma/diagnosis , Glaucoma/physiopathology , Humans , Image Processing, Computer-Assisted , Retina/physiopathology , Retinal Diseases/diagnosis , Retinal Diseases/physiopathology , Visual Acuity/physiology , Visual Fields/physiology
17.
Biochem Biophys Res Commun ; 442(3-4): 171-6, 2013 Dec 13.
Article En | MEDLINE | ID: mdl-24269822

A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.


Adenoviridae/physiology , Endostatins/genetics , Genetic Therapy/methods , Nasopharyngeal Neoplasms/therapy , Neovascularization, Pathologic/therapy , Oncolytic Virotherapy/methods , Oncolytic Viruses/physiology , Virus Replication , Adenoviridae/genetics , Animals , Carcinoma , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/blood supply , Oncolytic Viruses/genetics , Recombinant Proteins/genetics , Xenograft Model Antitumor Assays
18.
J Transl Med ; 11: 257, 2013 Oct 14.
Article En | MEDLINE | ID: mdl-24124726

BACKGROUND: Gene therapy using a recombinant adenovirus (Ad) encoding secretory human endostatin (Ad-Endo) has been demonstrated to be a promising antiangiogenesis and antitumor strategy of in animal models and clinical trials. The E1B55KD-deficient Ad dl1520 was also found to replicate selectively in and destroy cancer cells. In this study, we aimed to investigate the antitumor effects of antiangiogenic agent Ad-Endo combined with the oncolytic Ad dl1520 on gastric cancer (GC) in vitro and in vivo and determine the mechanisms of these effects. METHODS: The Ad DNA copy number was determined by real-time PCR, and gene expression was assessed by ELISA, Western blotting or immunohistochemistry. The anti-proliferation effect (cytotoxicity) of Ad was assessed using the colorimetry-based MTT cell viability assay. The antitumor effects were evaluated in BALB/c nude mice carrying SGC-7901 GC xenografts. The microvessel density and Ad replication in tumor tissue were evaluated by checking the expression of CD34 and hexon proteins, respectively. RESULTS: dl1520 replicated selectively in GC cells harboring an abnormal p53 pathway, including p53 mutation and the loss of p14(ARF) expression, but did not in normal epithelial cells. In cultured GC cells, dl1520 rescued Ad-Endo replication, and dramatically promoted endostatin expression by Ad-Endo in a dose- and time-dependent manner. In turn, the addition of Ad-Endo enhanced the inhibitory effect of dl1520 on the proliferation of GC cells. The transgenic expression of Ad5 E1A and E1B19K simulated the rescue effect of dl1520 supporting Ad-Endo replication in GC cells. In the nude mouse xenograft model, the combined treatment with dl1520 and Ad-Endo significantly inhibited tumor angiogenesis and the growth of GC xenografts through the increased endostatin expression and oncolytic effects. CONCLUSIONS: Ad-Endo combined with dl1520 has more antitumor efficacy against GC than Ad-Endo or dl1520 alone. These findings indicate that the combination of Ad-mediated antiangiogenic gene therapy and oncolytic Ad therapeutics could be one of promising comprehensive treatment strategies for GC.


Adenoviridae/metabolism , Antineoplastic Agents/therapeutic use , Endostatins/therapeutic use , Recombination, Genetic/genetics , Stomach Neoplasms/drug therapy , Viral Proteins/metabolism , Adenoviridae/drug effects , Adenovirus E1B Proteins/metabolism , Animals , Antineoplastic Agents/pharmacology , Cell Death/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Endostatins/pharmacology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Oncolytic Viruses/drug effects , Oncolytic Viruses/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/pathology , Treatment Outcome , Tumor Suppressor Protein p53/metabolism , Virus Replication/drug effects , Xenograft Model Antitumor Assays
19.
Fa Yi Xue Za Zhi ; 29(2): 96-8, 2013 Apr.
Article Zh | MEDLINE | ID: mdl-23930500

OBJECTIVE: To study the correlativity between the projected visual chart vision ("projector vision" in this paper) and the measured values of contrast vision, and to explore the application of contrast vision in identifying visual impairment after eye injury in the clinical forensic medicine. METHODS: One hundred and twenty nine eyes of seventy-nine young volunteers were collected for examination both of projector vision and contrast vision. In the examination of contrast vision, the contrast of optotypes were set to 100%, 25% and 10%, respectively. The correlativity of both collected experimental data were statistically analyzed. RESULTS: Projector vision was consistent with 100% contrast vision. There was a close and positive correlation between the contrast of optotypes and measured vision values. Under the same contrast of optotypes, projector vision presented a linear correlation with the average value of contrast vision. CONCLUSION: There is a close correlation between projector vision and contrast vision. The contrast vision can be applied to judicial identification in the clinical forensic medicine.


Contrast Sensitivity , Vision Tests , Visual Acuity , Adult , Eye Injuries/diagnosis , Female , Humans , Male , Middle Aged , Young Adult
20.
Fa Yi Xue Za Zhi ; 29(1): 5-11, 16, 2013 Feb.
Article En | MEDLINE | ID: mdl-23646494

In order to study the functional and structural alterations of the retina in SD rat model after methanol intoxication, 35 rats were divided randomly into five groups administrated with saline, 3-day high dose, 7-day high dose, 3-day low dose and 7-day low dose methanol separately. The retinal function of each group was assessed by flash electroretinogram (F-ERG) 3 and 7 days after methanol poisoning. The microstructure and ultrastructure of the retina were observed at the same time. The high-dose methanol intoxication induced irreversible retinal functional and structural damages 3 days after poisoning, which included prolonged latency and reduced amplitude of the Max-reaction of F-ERG. These injuries were aggravated 7 days after poisoning. Meanwhile, the latency and amplitude of the Cone-reaction of F-ERG were also affected 3 days after poisoning, but there were no further worsening tendency 7 days after poisoning. The retinal histological analysis showed cellular edema, heteromorphy and disarrangement, tissular loosen of the inner nuclear layer and photoreceptors layer. The mitochondrial damage began at the photoreceptors layer and developed further into the inner nuclear layer. The low-dose methanol intoxication only caused transient damage of the retina. Our results showed that the function and structure of the photoreceptor and inner nuclear layer were the primary target of methanol intoxication and that the rod cells were more sensitive to methanol intoxication than the cone cells. The mitochondrial damage developed from outer layer to inner layer of the retina.


Edema/chemically induced , Methanol/poisoning , Photoreceptor Cells/pathology , Retina/pathology , Animals , Edema/pathology , Electroretinography , Forensic Medicine , Male , Methanol/administration & dosage , Methanol/blood , Mitochondria/pathology , Random Allocation , Rats , Rats, Sprague-Dawley , Retina/physiopathology , Retinal Cone Photoreceptor Cells/pathology , Retinal Diseases/chemically induced , Retinal Diseases/pathology , Retinal Rod Photoreceptor Cells/pathology , Time Factors
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