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ABSTRACT: Along with the improvement of diagnostic techniques, hepatitis E has attracted increasing awareness in recent years. Hepatitis E virus infection leads to high mortality in pregnant women and patients with underlying liver disease. Several hepatitis E vaccine candidates have been designed and have proved their efficacy in animal models; two candidates have successfully undergone clinical trials. Having proved safe and effective in a large phase III trials, an Escherichia coli expressed particulate protein, HEV 239, has been registered in China and is now available for use in China.
Seminars in Liver Disease 02/2013; 33(1):79-88. · 7.05 Impact Factor
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ABSTRACT: There is emerging evidence for an under-recognized hepatitis E virus (HEV) as a human pathogen. Among different reasons for this neglect are the unsatisfactory performance and under-utilization of commercial HEV diagnostic kits; for instance, the number of anti-HEV IgM kits marketed in China is about one-fifth of that of hepatitis A kits. Over the last two decades, substantial progress has been achieved in furthering our knowledge on the HEV-specific immune responses, antigenic features of HEV virions, and development of serological assays and more recently prophylactic vaccines. This review will focus on presenting the evidence of the importance of HEV infection for certain cohorts such as pregnant women, the key antigenic determinants of the virus, and immunogenicity and clinical efficacy conferred by a newly developed prophylactic vaccine. Robust immunogenicity, greater than 195-fold and approximately 50-fold increase of anti-HEV IgG level in seronegative and seropositive vaccinees, respectively, as well as impressive clinical efficacy of this vaccine was demonstrated. The protection rate against the hepatitis E disease and the virus infection was shown to be 100 % (95 % CI 75-100) and 78 % (95 % CI 66-86), respectively.
Journal of Gastroenterology 11/2012; · 4.16 Impact Factor
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ABSTRACT: The first prophylactic vaccine, Hecolin®, against hepatitis E virus (HEV) infection and the HEV associated disease was approved by China's State Food and Drug Administration (SFDA) in December 2011. Key milestones during the 14-year HEV vaccine development are summarized in this commentary. After years of innovative research the recombinant virus-like particle (VLP) based antigen with virion-like epitopes was successfully produced in E. coli production platform on a commercial scale. Safety and efficacy of this vaccine was demonstrated in a large scale phase III clinical trial.
Human vaccines & immunotherapeutics. 06/2012; 8(6):823-7.
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ABSTRACT: There have been increased attentions on HEV and its associated diseases in recent years as a result of an increased number of reports on autochthonous patients from many developed countries. Vaccine development and better disease management are expected from protective immunity with increased knowledge on the pathogenesis and virology of HEV. This review summarizes the current understanding of the HEV virology, the key neutralization sites (epitopes) on the surface of the viral capsid, the host humoral immune responses for HEV infection, and the protective immunity conferred by natural infection and vaccination. Recombinant VLPs were prepared to mimic the protective and neutralizing epitopes on the virion surface, thus being capable of eliciting protective immunity when injected to nonhuman primates or human volunteers during preclinical tests and clinical trials. Four markers-viral RNA, anti-HEV IgM, anti-HEV IgG, and low avidity of anti-HEV IgG-are important in the diagnosis of HEV infection, particularly for patients presenting with acute hepatitis symptoms. This toolbox of genomic and immunological assays is valuable in furthering our understanding of the time course of HEV infection and the subsequent hepatitis during preclinical and clinical development of an efficacious vaccine. Two vaccine candidates had shown good tolerability, high immunogenicity, and high efficacy against symptomatic and/or asymptomatic HEV infection. One of them has been licensed in China recently. However, many issues need to be resolved before new technological progresses can benefit the people who need them most. Copyright © 2012 John Wiley & Sons, Ltd.
Reviews in Medical Virology 05/2012; 22(5):339-49. · 7.20 Impact Factor
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ABSTRACT: To study telomere length, senescence-associated-beta-galactosidase (SA-beta-galactosidase) and senescence marker protein-30 (SMP-30) in the stromal cells of keratoconus or normal corneas respectively, aiming finding the association of these indexes with the phenotype of keratoconus.
Experiment research. 37 keratoconus lesions corneas were removed from 32 keratoconus patients who were operated in Shangdong Eye Institute between January 2006 and December 2006, and 20 normal corneas were collected from eye bank. The keratoconus corneas ages were from 13 to 34 years [mean ages (19 + or - 5) years] and the control group consists of 20 normal corneas donor ages from 9 to 30 years [mean ages (19 + or - 4) years]. And there was no statistical difference of ages between keratoconus and normal corneas. Southern blot method was utilized to detect telomere length of genomic DNA. SA-beta-galactosidase was detected by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining method respectively in keratoconus and normal corneas. Isolated mRNA from keratoconus and normal corneas were reverse-transcribed to cDNA and SMP-30 was detected using PCR with specific primers (sense: 5' ccg tgg atg cct ttg act at 3'; anti-sense: 5' caa ctt cat gc tgct ttg ga 3'). To compare normal corneas and keratoconus corneas by histopathological study. Statistical analysis by t test.
The telomere length in stromal cells in keratoconus corneas were from 10.29 to 14.12 kb, mean (11.54 + or - 1.41) kb, while that of normal corneas were from 12.64 to 15.32 kb, mean (13.45 + or - 0.99) kb. The difference of telomere length in stromal cells of keratoconus and normal corneas reached a statistical significant level (t = 4.753, P < 0.05). That means the telomere length of keratoconus stroma was shorter than that of normal corneal stroma. Light microscopy revealed that collagen fibers in keratoconus corneal stroma were arranged in an irregular manner. Cells density in keratoconus stroma appeared lower than in normal ones but the decrease was not significant. The staining of SA-beta-galactosidase in the keratoconus section was evident, but there was no staining in the normal corneas. SMP-30 was not detectable with RT-PCR method in either keratoconus or normal corneas.
Telomeres in the keratoconus stromas manifest higher SA-beta-galactosidase than control, implying that improper senescence might be involved in pathogenesis of keratoconus.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 08/2009; 45(8):724-9.
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ABSTRACT: Endothelial keratoplasty (EK) is a new surgical method in treatment of corneal endothelial keratopathy, which retains healthy portions of a patient's cornea while replacing diseased endothelium with healthy donor tissue. In the past decade EK has been used increasingly and has shown better results over standard penetrating keratoplasty. The emergence and improvement of EK demonstrate the convert of corneal transplantation to refined and refractive surgery. EK, which has favorable refractive outcomes and potential low rejection rate, opens a new era for the treatment of endothelial dysfunction. However, there are still some aspects requiring to be studied, such as the methods of implantation to decrease graft dislocation rate and endothelial cell loss, use of femtosecond laser in EK to improve refractive errors, and the long-term result of immune rejection rate.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 01/2009; 44(12):1144-8.
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ABSTRACT: Phacoemulsification yields successful outcomes in eyes with standard cataract. Though techniques have been improved, it is still challenging to perform phacoemulsification in cases of hard cataracts for difficulty in nuclear management and much more complications. This study aimed at describing and evaluating the efficacy and safety of a peripheral radial chop technique to remove hard cataracts.
In this prospective study conducted between January 2003 and January 2004, 107 consecutive eyes with hard cataract underwent modified phacoemulsification surgery with peripheral radial chop technique by the Bausch & Lomb Millennium phacoemulsifier with preset parameters of power less than 30%; vaccum, 150 mmHg; and bottle height, 85 cm when a DP8145 phaco tip was used, and vaccum, 380 mmHg; bottle height, 95 cm when a DP8245 phaco tip was used.
The mean ultrasonic power was 14.7% (range 9% to 19%), ultrasonic time was 1.98 minutes (range 1.55 to 3.18 minutes). At 1, 7 and 30 days postoperatively, the eyes with uncorrected visual acuity 0.5 or better accounted for 76.42%, 87.16% and 90.67% respectively. At 1 month, the endothelial cell loss rate was 9.74% (range 8% to 17%). There were 6 cases of posterior capsule rupture in an early period of study. No serious intraoperative or postoperative complications were noted.
The peripheral radial chop technique was effective without serious complications in hands of an experienced surgeon.
Chinese medical journal 03/2007; 120(4):284-6. · 0.86 Impact Factor
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ABSTRACT: To analyze clinical features of keratoconus.
The case history of keratoconus patients who underwent penetrating keratoplasty, epikeratophakia or deep lamellar keratoplasty in our hospital during January 1993 to March 2002 was reviewed, and inquiry form was sent to those who without complete data. Patients were followed during January 2000 to March 2002. Two hundred and thirty three cases of keratoconus were enrolled in this study with 216 males and 17 females. Patient's family history, systemic complications, refractive status, progress of disease, eye axial length and anterior chamber depth were recorded.
The clinical natural history of these patients followed the model of "myopia-astigmatism-poor spectacle correction-acute corneal hydrops or stromal scar". The presenting age of myopia ranged from 6 to 29 years, with a mean age of 13.8 years, 10.1% (22/219) of the patients were younger than 10 years, 67.1% (147/219) were between 11 and 15 years. The interval time between emerging myopia and poor spectacle correction (best corrected visual acuity less than 20/200) was ranged from 1 to 20 years, of which 85.2% (161/189) were shorter than 6 years. Twenty percent (47/233) of the patients had acute corneal hydrops in one eye at the age of 12 to 31 years, and 4.3% of them (2/47) resulted in corneal perforation. Thirty-four patients had corneal stromal scars 1 to 13 years after keratoconus developed, and 94.1% of them (32/34) were within 8 years. Topography examination demonstrated a tendency of the cone base position progress: first, paracentral-enlargement following dominant astigmatism axis, then, enlargement along smaller astigmatism axis, and finally, the cone base moving centrally. The eye axial length averaged at (25.9 +/- 1.4) mm, the depth of anterior chamber (AC) were (4.3 +/- 0.3) mm, 89.7% (279/311) eyes had an axial length longer than 24 mm. All cases had an asymmetry clinical progress course. Two cases had Down syndrome, 2 with intelligence defect. No family history was noted in this study.
Keratoconus in Han nationality of Shandong Province has a relatively earlier age onset. These eyes tend to have a deeper AC with higher incidence of longer axial length.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 08/2005; 41(7):610-3.
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ABSTRACT: To evaluate the validity of confocal microscopy in estimating curative effect and in directing the treatment for fungal keratitis in the process of antifungal chemotherapy.
Fifty-eight patients, who were confirmed fungal infection by confocal microscopy, were selected from 328 patients with fungal keratitis. All patients received routine topical and/or oral antifungal medication, and were examined by confocal microscopy once a week and one week after discontinuation of the treatment. The density of hyphae in the corneal lesion, the configuration of inflammatory cells and keratocyte were recorded. Antifungal chemotherapy was adjusted according to examination results and medicines were changed accordingly. If no hyphae were detected by confocal microscopy, antifungal medication was maintained for one week and then discontinued. All patients were followed up for two months to ensure no relapse of fungal infection.
Fifty three patients were cured. The area of corneal lesions began to reduce 7 days after the beginning of antifungal chemotherapy. Confocal microscopy examination revealed that the hypha positive sites and the density of hypha were reduced gradually; inflammatory cells also decreased, the configuration of corneal lesion was transformed from asymmetry to symmetry; and normal keratocytes could be detected gradually. After 14 days of treatment, ulcers healed up in 37 cases and no hyphae and inflammatory cells were found in 23 cases. After 28 days of treatment, all corneal ulcers healed up; hyphae and inflammatory cells were completely disappeared in 31 patients, but a few hyphae still could be found in 22 patients. Antifungal chemotherapy was tapered gradually if no hyphae and inflammatory cells were detected by confocal microscopy. There was no relapse of fungus infection during 2-month follow-up. Infection deteriorated in the other five patients within 7 days, which showed increased density of hypha and inflammatory cells under confocal microscopy examination. All of them were treated with a penetrating keratoplasty to save the eyeball.
Confocal microscopy is an ideal method for the evaluation of curative effects of fungal keratitis in the process of antifungal chemotherapy. This is also a valuable objective tool in directing antifungal medication.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 08/2005; 41(7):614-9.
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ABSTRACT: To investigate the reasons why patients suffering hypermature or mature cataract in the urban Qingdao city do not undergo cataract surgery in time.
104 inpatients with mature or hypermature age-related cataract were interviewed with a questionnaire concerning medical, economic, social and psychological factors.
The factors related with the surgery delay were medical factor 44.3%, economic factor 7.1%, social factor 20.7% and psychological factor 27.9%. In the lists of detailed reasons, 'cataract being not mature' ranked the first (17.1%), 'unaware of cataract' (14.3%) and "still able to see something" (10.0%) were followed. The history of cataract surgery, age, degree of education, the knowledge of cataract and individual income all played some roles in the delay of cataract surgery (P < 0.05).
It is important to educate people about cataract knowledge and clarify the role of cataract surgery in order to convince patients to have cataract surgery done in time and improve life quality.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 03/2005; 41(3):205-10.
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ABSTRACT: To evaluate the influence of accurate diagnosis and peri-operative management on the recurrence of acanthamoeba keratitis after penetrating keratoplasty.
A retrospective study of 18 cases of medically unresponsive keratitis in Shandong Eye Institute and Hospital that were confirmed as acanthamoeba keratitis based on laboratory examination or histopathological studies. The diagnosis of acanthamoeba keratitis was made prior to the surgery in 12 cases and delayed until histopathological results in six cases. All cases ran a course of one to four months prior to penetrating keratoplasty with lesions measuring larger than 7 mm at the time of surgery. Corresponding anti-microbial agents were given pre-operatively based on the suspected etiological agents. Corticosteroids were given to two eyes diagnosed as acanthamoeba keratitis, three eyes misdiagnosed as herpes simplex keratitis and two eyes misdiagnosed as bacterial keratitis.
In 13 cases without recurrence (72%), 11 cases were correctly diagnosed as acanthamoeba keratitis prior to the surgery. In five cases with relapse (28%), four cases were misdiagnosed prior to the surgery. Seven cases received corticosteroid therapy more than one week in early post-operative period and four cases developed recurrence. In the four cases with relapse, two were misdiagnosed as herpes keratitis and two were misdiagnosed as bacterial keratitis. The odds ratis of the effect of two factors (misdiagnosis and using of corticosteroid in early post-operative period) on the rate of recurrence were 22 (P = 0.021) and 13 (P = 0.047), respectively.
Penetrating keratoplasty is an effective treatment for medically unresponsive acanthamoeba keratitis. Accurate pre-operative diagnosis, appropriate peri-operative amoebicidal therapy and avoidance from the use of corticosteroid in the early post-operative period can decrease the incidence of recurrence of acanthamoeba keratitis after penetrating keratoplasty.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 12/2004; 40(11):750-4.
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ABSTRACT: To study the drug concentration in the aqueous humor and the biocompatibility of cyclosporine A drug delivery system (CsA DDS) implanting in the anterior chamber.
There were four different types of CsA DDS which had different biodegradable polymers as the vector or had different ratio between CsA and the vector. Thirty-six New Zealand rabbits were randomly divided into 4 groups to receive the 4 different types of CsA DDS. Three of nine New Zealand rabbits received CsA DDS in one eye and empty DDS in the contralateral eye. Three rabbits received empty DDS in one eye and keratotomy in the contralateral eye. Another three rabbits received CsA DDS in one eye and keratotomy in the contralateral eye. All DDS were implanted into the anterior chamber. The follow-up period was 12 weeks.
No significantly acute or chronic intraocular toxic effects were found in all groups. The CsA release rate was different in these 4 groups. In type A and B CsA DDS, the drug released fast and maintained for a short period; in type C and D, the drug released slowly and could be maintained for a long period.
CsA DDS implanted in the anterior chamber can be well tolerated in rabbit eyes. CsA DDS is a promising approach for the prevention (type C and D CsA DDS) and treatment (type A and B CsA DDS) of corneal graft rejection.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 03/2004; 40(2):108-12.
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[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 12/2003; 39(11):703-4.
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ABSTRACT: To study the indication and incision of phacoemulsification and intraocular lens (IOL) implantation after high-risk penetrating keratoplasty (PKP) and to evaluate the clinical results.
Twenty-six eyes of 25 patients who underwent high-risk PKP were treated with phacoemulsification and IOL implantation. The high-risk reasons included chemical burn of cornea, severe infective corneal perforation, total keratoplasty, diameter of the corneal graft larger than 8.5 mm, secondary keratoplasty and PKP combined with cataract extraction and anterior segment vitrectomy. Systemic and local steroid administration was given and surgical indication and incision were chosen according to the condition of the eyes. The mean interval time between PKP and IOL implantation was 11 months. Visual acuity, refractive status, central corneal endothelial cell density before and after IOL implantation (3 months) and allograft rejection were recorded. The mean follow-up after IOL placement was 17 months.
Uncorrected visual acuity was 50/100 or better in 7 (27%) eyes and corrected visual acuity was 50/100 or better in 12 (46%) eyes. Fourteen (54%) eyes had refractive errors within 2 diopters. The mean refractive cylinders before and after IOL implantation were 5.70 D and 4.70 D, respectively (paired t test, t = 1.471, P = 0.154). The endothelial cell density before and after IOL implantation was 1883 cells/mm(2) and 1760 cells/mm(2), respectively (t = 1.934, P = 0.065) and the rate of endothelial cell loss was 6.5%. Only one graft rejection (4%) occurred 7 months after IOL implantation (anterior chamber IOL).
It is safe and effective to perform phacoemulsification and IOL implantation after high-risk PKP when paying attention to the perioperative treatment and selecting the surgical indication and the position of the incision.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 12/2003; 39(11):678-82.
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ABSTRACT: To investigate the cause of delayed diagnosis and treatment in severe fungal keratitis.
Retrospective analysis of the treatment history was performed in patients with severe fungal keratitis which attended to our hospital during 2000 to 2001. The main parameters evaluated were nature of access with the health care services, examinations undertaken, initiated treatment, and the time interval between presentation to each medical contact and to our center. Finally, the management undertaken at our center was evaluated.
69 patients (eyes) were enrolled into this investigation, of which 86% (59/69) was local residents in Shandong province, 93% (64/69) was farmer. Penetrating keratoplasty (PKP) were performed for 63 cases with a transplantation of donor cornea > 8.0 mm. However, 6 eyes were enucleated because of the severe endophthalmitis. Most of patients sought medical care following a same procedure: village and towns medical service, county hospital, city medical center. The time interval between the first medical contact and presentation to our center was 22.9 days on average. 78% (54/69) patients attended to county hospitals, only 24% (13/54) patients got correct diagnosis of fungal keratitis. Smear examination had been undertaken only in 22% (12/54) of cases, the positive rate was 50%. In 30 patients who initially contact to city medical centers, 63% (19/30) was diagnosed as fungal keratitis, 73% (22/30) was given smear examination with positive result of 73% (16/22). The positive rate of corneal scraping for fungus was 93% (64/69). 46% (35/69) patients were prescribed antifungal agents of fluoconazole.
Several factors, including ignoring traumatic history and basic examination techniques, lacking of effective ophthalmic antifungal agents, cornea donor, without qualified ophthalmologists, lead to inappropriate management in fungal keratitis.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 05/2003; 39(5):274-7.
