Objective: To study the permeability of leflunomide and the effect of liposome on its permeability. Methods: Modified Franz diffusion cell adopted as apparatus for in vitro skin permeation. Various excised skins were used as permeation barriers and permeation coefficient was used as index. The concentration of leflunomide in the samples was measured by HPLC. Results: Leflunomide had a good permeability, but the effect of liposome on permeability was not very strong. Conclusion: It is feasible that leflunomide is applied through skin. [

OBJECTIVE:To establish the RP-HPLC method for determination of methyl hydroxybenzoate and ethyl hydroxybenzoate in oral liquid preparations METHODS:The Nova-Park C18 column(3 9mm?150mm,5?m)was used The mobile phase consisted of acetonitrile-water(25∶75)at a flow rate of 1ml/min,the detection wavelength was set at 254nm and the sensitivity was set at 0 01 AUFS RESULTS:The linear ranges of methyl hydroxybenzoate and ethyl hydroxybenzoate were 0 4 412～13 2 360?g/ml(r=0 9 999) and 0 6 672～20 0 160?g/ml(r=0 9 998)respectively CONCLUSION:The method is simple,rapid and accurate It can be used to detect antiseptics in hospital preparations

ObjectiveTo determine a measurement standard of irregular scar area by comparing the ad-vantages and disadvantages of different measurement methods in measuring same irregular scar area. MethodsIrregular scar area was scanned by digital scanning and measured by coordinate reading method, AutoCAD pixel method, Photoshop lasso pixel method, Photoshop magic bar filled pixel method and Foxit PDF reading software, and some aspects of these methods such as measurement time, repeata-bility, whether could be recorded and whether could be traced were compared and analyzed.Results There was no significant difference in the scar areas by the measurement methods above. However, there was statistical difference in the measurement time and repeatability by one or multi performers and only Foxit PDF reading software could be traced back.ConclusionThe methods above can be used for measuring scar area, but each one has its advantages and disadvantages. It is necessary to develop new measurement software for forensic identification.

Objective To observe the effects of penetrance,different time of onset and mutation sites on retinal nerve fiber layer (RNFL) and macular thickness in patients with Leber's hereditary optic neuropathy (LHON).Methods This was a cross-sectional observational study.A total of 88 patients with LHON and 1492 relatives of the maternal relatives (gene carriers) who received treatment in People's Liberation Army General Hospital from 2015 to 2017 were included in the study.Among the 1492 family members,there were 694 males and 798 females.Peripheral venous blood was extracted from all subjects for mitochondrial DNA testing,and penetrance was calculated.A total of 117 patients underwent BCVA and SD-OCT examinations,including 82 patients and 35 gene carriers.The BCVA examination was performed using the Snellen visual acuity chart,which was converted into logMAR visual acuity.The thickness of RNFL,ganglion cell complex (GCC) and inner limiting membrane (ILM)-RPE were measured with OCT instrument.The mean follow-up was 50.02± 86.27 months.The disease course was divided into 6 stages including ≤3 months,4-6 months,7-12 months and ＞ 12 months.The thickness of RNFL,GCC and ILM-RPE in patients with different time of onset and mutation sites were comparatively analyzed by covariance analysis.Categorical variables were expressed as a percentage,and the x2 test was used for comparison among multiple groups.Results Among the 1492 family members,285 were diagnosed with LHON and highly suspected clinical manifestations (19.10％),including 190 males (21.98％) and 95 females (11.90％).The total penetrance rates of 11778,14484 and rare mutation sites were 19.84％ (228/1149),20.50％ (33/161),and 13.19％ (24/182) respectively;male penetrance rates were 28.87％ (153/530),27.28％ (20/72),and 18.48％ (17/92) and female penetrance rates were 12.12％ (75/619),14.61％ (13/89) and 7.78％ (7/90).There was no significant difference in total (x2=4.732),male (x2=4.263) and female (x2=4.263) penetrance between different mutation sites (P=0.094,0.110,0.349).Compared with non-pathogenic carriers,the thickness of the RNFL,GCC and ILM-RPE were all different in the four stages (≤3months,4-6 months,7-12 months and ＞12 months).The thickness ofRNFL,GCC and ILM-RPE decreased with the time of onset (P=0.000).There were significant differences in the thickness of each of the GCC and ILM-RPE layers in the macular area of LHON patients with different mutation sites (P＜ 0.05).Among them,the site 11778 and 3460 had the most severe damage in all quadrants of macular GCC and ILM-RPE layer,followed by 14484 site,and the rare site had the least damage in all quadrants.Conclusions The penetrance of LHON patients is 19.10％.With the extension of the onset time (within 1 year),the RNFL layer of the optic disc and all quadrants of the macular GCC and ILM-RPE layer gradually thinned.Compared with 11778 and rare site,14484 site,and the rare site had the lighter damage on the thickness of RNFL,GCC and ILM-RPE.

Objective To understand the situation of knowledge,attitude and practice (KAP) of sheep farmers and field veterinarians towards brucellosis prevention,and find out the potentially influential factors.Methods From March to September in 2017,1 067 sheep farmers and 401 field veterinarians were selected as participates,and questionnaire survey was carried out.Percentage rate was used to describe the situation of KAP.Nonparametric test was used to compare the KAP score difference.Results The overall awareness in sheep farmers and field veterinarians was 64.2％ and 80.1％,respectively.In addition,there were 17.3％ (185/1067) sheep farmers and 12.2％ (49/401) field veterinarians had never heard of brucellosis.The knowledge awareness in sheep farmers and field veterinarians was 62.6％ and 79.0％,respectively,75.8％ and 83.8％ of them had positive attitude to brucellosis prevention,54.1％ and 77.6％ of them had good practice habit.They hoped in the future,more information could be received through TVs,and then was internet or broadcasting.Sheep farmers who from first class region,age less than 45 years,education higher than junior high school,feeding time less than 5 years and sheep ever infected with brucellosis (U =4.85,3.08,3.29,2.20,6.62,P ＜ 0.05 or ＜ 0.01),had higher KAP scores than others.Field veterinarians,who had lower education,had lower KAP scores (U =4.29,P ＜ 0.01).Conclusions The awareness of sheep farmers and field veterinarians still need to improve and strengthen.Some suggestions are put forward:improve intervention pattern,optimize content and method,pay attention to use new media.

The first edition of "The Chinese expert consensus on the diagnosis and treatment of optic neuritis" have been published in Chinese Journal of Ophthalmology in 2014. Seven years later, more evidence-based medicine has been accumulated in the treatment of optic neuritis. It is necessary to update or formulate guidelines to guide clinical practice. Based on the methods and procedures for developing evidence -based guidelines, Neuro-Ophthalmology Group of Ophthalmology Branch of Chinese Medical Association and Evidence-based Medicine Centre of Lanzhou University/World Health Organization Collaborating Centre for Guideline Implementation and Knowledge Translation created the first "An evidence-based guideline for the diagnosis and treatment of demyelinating optic neuritis in China (2021)" , which aimed to improve the level of clinical diagnosis and treatments of demyelinating optic neuritis. This guideline proposes a new subtype classification of demyelinating optic neuritis to guide precision treatment. It also gives new suggestions about clinical treatment hotspots in the acute and chronic phases, including the application of immunosuppressants and rituximab and other biological agents.

Objective:To observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).Methods:A cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid(mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow- up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression. Results:Thirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow- up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation( P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027). Conclusions:EON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery.

Objective:To observe the clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON).Methods:A retrospective case series. Twenty-three eyes of 14 children with AQP4-PON who were clinically confirmed in the Department of Ophthalmology of the First Medical Center of the Chinese PLA General Hospital from January 2015 to December 2018 were included in the study. All patients underwent BCVA, fundus color photography, and magnetic resonance imaging (MRI). OCT was performed on 15 eyes of 10 patients, and the peripapillary retinal nerve fiber layers (pRNFL), macular ganglion cell-inner plexiform layers (mGCIPL) thickness of the affected eyes were measured. Cell-based indirect fluorescent immunoassay was used to detect serum AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. The follow-up time ranged from 28 to 59 months. The clinical, neuroimaging characteristics and prognosis of the children were analyzed.Results:Among 14 children, 2 were male (14.3%) and 12 were female(85.7%). The mean age of onset was 13.3±3.0 years. On the first visit, there were 10 unilateral patients and 4 bilateral patients. The first manifestations were 11 patients of optic neuritis (78.6%), 2 patients of posterior pole syndrome (14.3%), and 1 patient of myelitis (7.1%). There were 10 patients (71.4%) with eye pain, and 5 patients(35.7%) combined with autoantibodies positive. When the first onset time was less than 2 weeks, fundus examination revealed disc edema in 7 eyes (38.9%). After 3 months, the average pRNFL and mGCIPL thickness of 15 eyes underwent OCT examination were 62.33±11.07 and 54.17±5.42 μm, respectively. Orbital MRI showed that the optic nerve showed a long T2 signal in 14 patients (100.0%) and 11 patients (78.6%) with T1 intensive lesions. When the first onset was less than 2 weeks, 16 eyes (88.9%) had BCVA≤0.1, and 7 eyes(38.9%) had BCVA≤0.1 and 9 eyes (50.0%) with BCVA≥0.5 after glucocorticoid treatment. Recurrence occurred in 11 patients during follow-up and was treated with immunosuppressive agents. At the last visit, in 14 patients, 9 eyes (64.3%) were involved in both eyes, and 5 patients (35.7%) progressed to neuromyelitis optica; in 23 eyes, 8 eyes (34.8%) had BCVA≥0.5.Conclusions:AQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica.

Objective:To investigate the clinical, laboratory and imaging evaluation, treatment and prognosis of patients with idiopathic hypertrophic pachymeningitis (IHP) with ophthalmic manifestations as the first symptom.Methods:A retrospective case analysis. Eight patients displaying symptoms of IHP were recruited from the Neuro-ophthalmology Department in the First Medical Center of Chinese PLA General Hospital from January 2016 to April 2019 were inculed in this study. There were 6 males and 2 females, aged from 11 to 65 years, with an average age of 48.00±19.08 years. The course of disease ranged from 30 days to 7.5 years, with an average course of 17.00±30.08 months. The age, symptoms and signs of all patients were recorded. All patients underwent ophthalmic examination, orbit or brain MRI or CT examinations, blood routine examination, biochemistry, tumor markers, immunity, hepatitis B, syphilis, HIV, thyroid function and other laboratory tests, and lumbar puncture was performed to measure the cerebrospinal fluid (CSF) pressure and indicators. The clinical manifestations, orbital or brain MRI imaging and laboratory examination characteristics were summarized. Treatment and prognosis were also observed.Results:In total of 8 patients, visual loss was presented in 6 patients, visual loss and diplopia were presented in 1 patient, and diplopia was presented in 1patient. Binocular involvement in 7 patients and monocular involvement in 1 patient. Other symptoms including headache and hear loss and so on. Optic disc edema in 1 eye and optic disc pallor in 6 eyes were reviewed by fundus examination. The laboratory examination showed that the angiotensin converting enzyme abnormal in 4 patients, the anti-thyroid peroxidase antibody abnormal in 3 patients and immunoantibodies positive in 3 patients. CSF measurements showed that the protein level elevated in all patients. Orbit and/or brain MRI and CT examination showed that optic nerve involvement in 6 patients, oculomotor nerve involvement in 1 patient, and cavernous sinus region involvement in 2 patients. Glucocorticoid was effective in all patients, and the visual acuity significantly improved in 4 patients, the diplopia was completely resolved in 2 patients, and the disease modifying therapy (DMT) was combined to prevent recurrence in 7 patients. No recurrence was observed in an average follow-up time of 26.63±16.55 months.Conclusions:IHP patients may be first visit an ophthalmologist due to vision loss in bilateral eyes simultaneous or sequentially. IHP patients are often associated with headache and other cranial nerve paralysis symptoms. Definitive diagnosis of IHP depends on imaging examination. Glucocorticoid treatment is effective in early phase, but it is tendency to progress and relapse, suggesting combined with DMT as early as possible.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.