1.Safety and efficacy of mitomycin nanoparticles in inhibiting scar proliferation after glaucoma filtration surgery
Ying LI ; Juan TANG ; Changfen LI ; Qilin FANG ; Xingde LIU ; Dan ZHANG ; Tingting ZHANG ; Xiaoli WU ; Tao LI
International Eye Science 2024;24(11):1708-1714
AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.
2.A pilot molecular mechanism study on lacrimal gland as a potential human immunodeficiency virus reservoir
Ziyang, LIU ; Xiaowei, LIU ; Junjie, YE ; Yang, HAN ; Zhen, HUO
Chinese Journal of Experimental Ophthalmology 2017;35(5):410-415
Background Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by human immunodeficiency virus (HIV).Highly active antiretroviral therapy (HAART) is an effective treatment for AIDS,but it cannot completely eliminate the viral load in the body for the existence of HIV reservoir.Previous studies demonstrated that HIV could be detected in tears of virus load negative AIDS patients who received effective HAART,suggesting that lacrimal gland is another member of HIV reservoirs.Objective The aim of this study was to explore whether lacrimal gland has a molecular basis of HIV infection and the mechanism of lacrimal gland infection of HIV.Methods Fourteen specimens of lacrimal gland were collected during the surgery from 14 patients with lacrimal gland diseases in Peking Union Medical College Hospital from November 2013 to December 2015,including 13 non-HIV-infected patients and 1 HIV-infected patient.In 13 non-HIV infected patients,lacrimal glands prolapse was in 12 patients with the normal pathological tissue structure and dacryoadenitis was in 1 patient with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The clinical manifestation of HIV-infected patient was dacryoadenitis with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The paraffin sections of 12 non-HIV-infected specimens and 1 HIV-infected specimen were prepared,and the expressions of CD4,C-X-C chemokine receptor 4 (CXCR4) and C-C chemokine receptor type 5 (CCR5) in lacrimal gland specimens were detected by immunohistochemistry and verified in 1 specimen of non-HIV-infected specimen by immunofluorescence technology.Results Immunohistochemistry showed that CD4 was suspiciously positive expression in non-HIV-infected specimens with the strong background staining.CXCR4 was positively expressed in cytoplasm and nuclei of most lacrimal epithelial cells of lacrimal gland epithelial cells in each specimen,and CCR5 was focally expressed in few lacrimal gland epithelial cells in each specimen.In addition,CD4,CXCR4 and CCR5 were positively expressed in intercellular scattered lymphocytes on the specimens.Immunofluorescence assay showed that CD4,CXCR4 and CCR5 were expressed in the specimens with the red fluorescence,with the linear-and patchy-like distribution mainly in cellular membrane for CD4 or spot-like distribution for CXCR4 and CCR5 in the cytoplasm.Conclusions HIV receptor CD4 and accessory receptor CXCR4,CCR5 are positively expressed in the lacrimal gland epithelial cells,which is the molecular basis of HIV infection and become a potential HIV reservoir preventing HIV eradication.
3.Biomechanical study on the impact injure of human mandible by finite element method
Ziyang YANG ; Songbo QIU ; Yu LIU ; Po WU ; Yinghui TAN
Journal of Practical Stomatology 2016;32(3):377-382
Objective:To investigate biomechanical changes of mandible in the impact injure simulated by finite element method (FEM).Methods:Mimics and Comsol software were used to build a FEM of human craniofacial bone based on CT scan data of a normal adult.LS-DYNA and Hypermesh software were used to simulate the impact with different quality,velocity and angulation pro-duced injures of human mandible,the biomechanical parameters of the mandible in the impact injury process were analysed.Results:A FEMof human maxillofacial bone was established,and the dynamic process of different impact force produced damage was simula-ted.Mandibular chin,angle and condylar neck was the stress concentrated area in the process of mandible injury.There was higher stress peak at the site which was closer to the impact position,the stress peak arrival time was also earlier.When the impactor with the same quality,the bigger the velocity,the greater the stress peak.When the impactor with the same velocity,the bigger the quali-ty,the greater the stress peak.When the impactor with the same velocity and quality,there was greater stress peak under the impact to mandible from angulation of 0 degree.Stress transfered to the surrounding bone from the impact position radially and gradually re-duced.The bone area with small cross-section was prone to high stress and more serious damage.Conclusion:The quality,the ve-locity,the impact angle and the impact site are the factors affecting the severity of impact injury.
4.Multi-band mucosectomy for early esophageal cancer and precancerous lesions
Xiaogang LIU ; Ziyang CHEN ; Yi LI ; Yunchao YANG ; Renyi ZHANG ; Liangping LI
Chinese Journal of Digestive Endoscopy 2012;29(7):397-401
Objective To evaluate the safety and efficacy of multi-band mucosectomy (MBM) for early esophageal cancer and precancerous lesions.Methods Data of 28 patients with early esophageal cancer or precancerous lesions undergoing MBM were reviewed in regarding of procedure complications and follow-up results.Results A total of 32 lesions were resected successfully by MBM in one session,with mean procedure time of 28.3 minutes.The mean diameter of specimens was 12mm.No residual neoplasm was found at the base of any resected specimens.The post-MBM pathological findings consisted of 2 cases of intramucosal cancer,1 case of submucosal cancer,and 25 cases of moderate-severe dysplasia.No perforation,delayed hemorrhage or subcutaneous emphysema occurred.Intraoperative bleeding occurred in 23 cases,including 3 cases of pulsatile bleeding,which were controlled with metal clip,and 20 cases of minor bleeding which were managed with APC or halted automatically at the end of procedure.Chest pain after the procedure occurred in 5 cases and were relieved soon.The patient with submucosal cancer underwent subsequent surgical resection,with no residual cancer in surgical specimen or lymph node metastasis.Twenty seven other cases were followed up endoscopically for 2-12 months.Esophageal stricture occurred in 2 cases,and were successfully relieved by dilatation with stent or bougienage.No recurrent lesion or metastasis were revealed.Conclusion MBM is a relatively safe and effective endoscopic technique for treatment of early esophageal intramucosal cancer and precancerous lesions,but further studies are needed to evaluate the long-term results.
5.Contrast-enhanced ultrasound characteristics of choroidal hemangioma
Haicheng, SHE ; Dongjun, LI ; Wenli, YANG ; Wei, CHEN ; Ziyang, WANG ; Wenbin, WEI
Chinese Journal of Experimental Ophthalmology 2015;33(1):51-54
Background Choroidal hemangioma is a common benign intraocular tumor.Typical choroidal hemangioma is comparably easy to diagnose,but untypical one might be misdiagnosed as malignant tumor.Contrastenhanced ultrasound (CEUS) has been used to diagnose multiple neoplasm for the past few years.However,the application of CEUSin ophthalmology is less.Objective This study was to investigate the CEUS characteristics of choroidal hemangioma.Methods Fifty-eight eyes of 58 patients who were diagnosed as choroidal hemangioma were included in Beijing Tongren Hospital during July 2010 to December 2012.CEUS was performed on the patients to check the manifestations of choroidal hemangioma.A time-intensity analysis was employed to quantitatively analyzed and compared the maximum intensity (MI),rising time (RT),time to peak (TTP),and mean transit time (mTT) between the choroidal hemangioma and normal orbital tissue and the parameters were contrasted using Wilcoxon signed-rank test.Results CEUS showed that choroidal hemangioma was gradually enhanced by the contrast after intravenous injection of sulphur hexafluoride microbubbles with a high-reference signal in choroidal hemangioma,and the fading procedure was slower in choroidal hemangioma than that of normal orbital tissue.MI,RT,TTP,and mTT were294.20% (217.35%,373.25%),21.30 (17.35,23.35) s,25.00 (21.68,27.48) s and 59.30 (51.08,78.35) s in the choroidal hemangioma,which were significantly higher than 100.00% (100.00%,100.00%),17.75 (15.00,20.30) s,22.40 (18.35,24.63) s and 47.25 (40.90,57.23) s in the normal orbital tissue (Z =-6.608,-4.998,-4.650,-4.332,all at P<0.001).Conclusions Choroidal hemangioma has its own CEUS manifestation characteristics.CEUS is helpful to the differential diagnosis of choroidal hemangioma.
6.Experimental study on establishment of a 3D finite element model of human craniomaxillofacial region and its use in impact injury simulation
Yu LIU ; Ziyang YANG ; Po WU ; Gang ZHANG ; Songbo QIU ; Yinghui TAN
Chinese Journal of Trauma 2016;32(2):161-165
Objective To develop a 3D finite element model for the human craniomaxillofacial region in an attempt to offer basis to the research of simulation of craniomaxillofacial injury.Methods A healthy adult male was submitted to head CT scan, and the data was imported into the Mimics 15.0 software for threshold segmentation and 3D reconstruction according to the classifications of bone tissue, skin tissue and subcutaneous tissue.The reconstruction data was imported into 3D reverse software Geomagic Studio 2012, and the images were optimized and the 3D model was generated.The three parts of the model were fitted according to the actual proportion using the 3D control software Solidworks 14.0, and then the boundary conditions were derived.Hypermesh 12.0 finite element processing software was used to build the volume mesh, and the model was established.Each layer of the model was given to the material parameters, and the simulation conditions were provided to test the model.Results This model was completely composed of volume meshes, including 214,250 hexahedral meshes and 411,920 nodes.This model can clearly show the stress distribution, the trend of fracture line, the displacement of fracture block of soft and hard tissue during the simulation, and the results are consistent with clinical practice.Conclusion A three-dimentional finite element model with good performance is established, which can be used for biomechamics simulation analysis of multiple sites on the head or the whole structure, and has a certain significance in clinical and scientific research.
7.Study of direct identification of pathogens from positive blood cultures by methods of separation gel tube -centrifugation
Chenrui HOU ; Yun YANG ; Ziyang LI ; Chunyan GAO ; Miao SU ; Chaojun LANG
Chinese Journal of Primary Medicine and Pharmacy 2016;23(14):2119-2122
Objective To study the possibility of direct identification of pathogens from positive blood cul-tures by methods of separation gel tube -centrifugation.Methods 216 cases of positive blood culture were collected from 2015.7 to 2015.12.The bacterias were purified from blood culture bottle by separation gel tube.After washing 2 times,identified by MALDI -TOF MS.At the same time,traditional culture,smears and identification were done. Compared the results of identification by two methods.Results 216 cases of positive blood culture were single bacte-rial infection.By Gram stain,89 strains were Gram positive,119 strains were Gram negative and 8 strains were fungal spores.190 cases of positive blood culture were identified by MALDI -TOF MS,it concluded 67 Gram positive strains,111 Gram negative strains,4 anaerobe strains and 8 fungus.Compared with traditional culture,the coincidence rate reached up to 87.9%,Gram positive strains 78.8%,Gram negative strains 93.2%,anaerobe strains 100.0%and fungus 100.0%.Conclusion It takes less than 30 minutes purified from blood culture bottle by separation gel tube.And the time of identification is shorter than traditional culture.This method is good for clinical diagnosis and treatment.
8.Ultrasound diagnosis and analysis of intraocular cysticercosis
Ziyang WANG ; Dongjun LI ; Wei CHEN ; Qi ZHAO ; Yifeng LI ; Wenli YANG
Chinese Journal of Ultrasonography 2015;(7):606-609
Objective To investigate the characteristic of the B-mode ultrasonography and the color Doppler flow imaging diagnosis for intraocular cysticercosis.Methods Eleven eyes of 1 1 patients diagnosed of intraocular cysticercosis clinically and confirmed by operation and pathology were retrospectively studied. Their B-mode ultrasonography and color Doppler flow imaging were analyzed.Surgery diagosis was also reviewed.Results Among 1 1 eyes of 1 1 patients,intravitreal cysticercus presented in 7 cases (7 eyes),and 4 cases (4 eyes)diagnosed of subretinal cysticercus.Intraocular cysticercosis showed a round or oval vesicle-like echogenic mass in the vitreous body or under the retina,and the high-level echo spot in it was the scolex. Some dot and stripe echo and retinal detachment also appeared in the vitreous cavity with vitreous inflammation.The blood flow signal was detected in retinal detachment with color Doppler flow imaging. Conclusions Ultrasonography is extremely useful in the diagnosis of intraocular cysticercosis and the findings can be pathognomonic.
9.Effect of antiviral therapy on long-term prognosis of patients with decompensated hepatitis B cirrhosis
Journal of Clinical Hepatology 2016;32(6):1104-1107
ObjectiveTo investigate the effect of antiviral therapy on the long-term prognosis of patients with decompensated hepatitis B cirrhosis. MethodsA total of 132 patients with decompensated hepatitis B cirrhosis who were hospitalized in The People′s Hospital of Lezhi County 3 times or more from May 2009 to May 2012 were enrolled in the study. According to the therapies, the patients were divided into control group (51 patients) and observation group (81 patients). All the patients were followed up for 5 years via outpatient service and by telephone. Child-Pugh score and Model for End-Stage Liver Disease (MELD) score were obtained from all patients, and the reduction in HBV DNA, HBV DNA clearance, and liver function parameters were observed. Clinical outcomes were compared at the end of follow-up between the two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe observation group had significantly lower incidence rate of liver cancer, rate of liver transplantation, and mortality rate than the control group (χ2=4.32, 4.33, and 4.71, all P<0.001). After treatment, the observation group showed a significant reduction in HBV DNA level (t=20.60, P<0.001) and had a significantly lower HBV DNA level than the control group (t=16.40, P<0.05). After treatment, the observation group had a significantly higher cumulative clearance rate of HBV DNA than the control group (88.89% vs 6.67%, P<0.05). After treatment, the observation group had a significantly higher serum albumin level and significantly lower levels of total bilirubin (TBil) and alanine aminotransferase (ALT) than the control group (t=6.77, 16.60, and 11.67, all P<0.001), and both groups showed significant reductions in TBil and ALT after treatment (observation group: t=25.18 and 23.33, both P<0.001; control group: t=6.15 and 7.20, both P<0.001). The observation group showed a significant increase in serum albumin level after treatment (t=10.08, P<0.001). After treatment, the observation group had significantly lower Child-Pugh score and MELD score than the control group (t=2.27 and 2.24, both P<0.05), both groups showed significant reductions in Child-Pugh score and MELD score (observation group: t=9.18 and 8.17, P<0.001 and P=0.03; control group: t=2.93 and 3.12, P=0.01 and 0.04). ConclusionLong-term antiviral therapy can improve the long-term prognosis of patients with decompensated hepatitis B cirrhosis and increase the 5-year survival rate.
10.Study on the role and mechanism of osteogenesis induced by advanced platelet-rich fibrin and β-tricalcium phosphate complex
FU Dongmei ; ZHOU Jing ; WANG Lang ; YANG Xin ; LAN Hong ; LI Sulan ; WANG Jin ; FANG Jie
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(4):237-244
Objective :
To investigate the role and mechanism of bone formation caused by the ratio of advanced platelet-rich fibrin (A-PRF) and β-tricalcium phosphate (β-TCP) in rabbit femur defect model, which provides a new idea for clinical treatment of bone defect.
Methods :
Twenty-four New Zealand white rabbits were divided into model group, 1∶1 complex group (A-PRF∶β-TCP=1∶1), 2∶1 complex group (A-PRF∶β- TCP=2∶1) and 4∶1 complex group (A-PRF∶β- TCP=4∶1), with 6 rabbits in each group. Femoral defect models were constructed in each group. In the composite group, the bone defect was filled with composite material, while in the model group, no material was filled. After 8 weeks, the animals were euthanized and specimens were collected. Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.SP) and trabecular number (Tb.N) in femoral defect tissue were measured by micro-CT and photographed. Hematoxylin - eosin staining was used to detect the pathological changes of new bone tissue. The morphological changes of the new bone tissue were observed by scanning electron microscopy. Determination of phospho-mitogen activated protein kinase p38 (p-p38MAPK), CCAAT/enhancer binding protein homologous protein (CHOP) and phospho-cysteine aspartic protease-3 (p-Caspase3) in newborn femur by ELISA. The mRNA expressions of osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor kappa-B ligand (RANKL) and p38MAPK were detected by real-time quantitative PCR. The expression of OPG, BMP-2, RANKL, p-p38MAPK and p-Caspase3 protein in the new bone tissue was observed by immunohistochemistry.
Results :
In the model group, bone formation in the femoral defect area was slow and osteogenic quality was poor. Compared with the model group, the bone formation and neocapillaries of femoral defect area in the complex group was good, BMD, BV.TV, Tb.Th, Tb.N were increased, and Tb.Sp were decreased, the expressions of p-p38MAPK, CHOP and p-Caspase3 were decreased, and the mRNA and protein expressions of OPG and BMP-2 were increased. The mRNA expression of RANKL and p38MAPK was decreased. Apoptosis in new bone tissue of each group showed the lowest apoptosis rate in samples of the 2∶1 complex group (P<0.05); A-PRF: β-TCP=2∶1 ratio has the best osteogenic effect.
Conclusion
The complex composed of A-PRF and β-TCP can promote the expression of OPG, inhibit the expression of RANKL and phosphorylation of p38MAPK, reduce the apoptosis of new bone tissue cells, and promote osteogenic differentiation.