VPS13B gene variation and clinical phenotype of Cohen syndrome in a Chinese Han family / 中华实验眼科杂志

Objective:To analyze the pathogenicity and clinical characteristics of patients with Cohen syndrome caused by a compound heterozygous variation of VPS13B gene. Methods:A pedigree investigation was conducted.A Chinese Han family with Cohen syndrome was recruited from Henan Eye Hospital in September 2021.There were three members of two generations in this family, including one patient.The clinical data of the proband and his parents were collected, and the relevant ophthalmic and general examinations were performed to evaluate the clinical phenotype.The peripheral venous blood samples of the family members were collected to extract whole genomic DNA, and the whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were performed among the family members.According to the ACMG guidelines, the pathogenicity of the selected variants was evaluated and the online tools were used to predict the pathogenicity of the variants.Relevant literature of Cohen syndrome were retrieved in Online Mendelian Inheritance in Man (OMIM) and PubMed, China National Knowledge Infrastructure and Wanfang databases by taking Cohen syndrome and VPS13B gene as the searching keywords.The clinical manifestations and pathogenic variants of patients in the literature were summarized, and the relationship between genotype and clinical phenotype was analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). Both the subject and the patient's guardian were aware of the study purpose and method.Written informed consent was obtained. Results:The family was consistent with autosomal recessive inheritance.The proband, a 5-year-old male, had bilateral night blindness with photophobia, ptosis, lower eyelid entropion, and trichiasis; high myopia in both eyes; osteoblastoid pigmentation in the peripheral retina, atrophy and thinning of the outer layer of the peripheral retina, extinguished flashing electroretinogram; global growth retardation, typical facial features, slender fingers and toes, flatfoot, foot valgus, dystonia, no cardiac abnormalities; excessively cheerful personality.The clinical manifestations of the proband were consistent with Cohen syndrome.No obvious abnormality was found in the clinical phenotype and the auxiliary examination of the proband's parents.Whole exon sequencing revealed that the proband carried two heterozygous variations, a nonsense variation c. 11713C>T(p.Gln3905*) and a splicing variation c. 6940+ 1G>T.Sanger sequencing confirmed that the above variations were co-segregated in this family.c.11713C>T(p.Gln3905*) was a novel variant, which prematurely terminated the protein encoded by it and affected the normal function of the protein.The two variations were pathogenic variants according to the ACMG guidelines.A total of 12 articles on variants and clinical characteristics of Cohen syndrome in China were retrieved.Combined with the results of this study, a total of 24 VPS13B variants were found in Chinese patients, of which the incidence of frameshift variation was 41.7%(10/24), missense variation 20.8%(5/24), splicing variation 20.8%(5/24) and nonsense variation 16.7%(4/24), respectively.The onset age of patients with Cohen syndrome was from 28 days to 12 years old.The symptoms such as nerve system, eye, brain, and bone were sporadic, and the clinical manifestations were highly heterogeneous. Conclusions:A novel pathogenic variation c. 11713C>T is found in the VPS13B gene of the Cohen syndrome pedigree in this study, and expands the pathogenic variation spectrum of the VPS13B gene.The clinical manifestations of Cohen syndrome are highly heterogeneous.

Comparison of detection rates and time costs of different fundus imaging techniques for retinal neovascularization in optic disc and other area of proliferative diabetic retinopathy / 中华实验眼科杂志

Objective:To compare the detection rate and time cost of different imaging methods for retinal and optic disc neovascularization in proliferative diabetic retinopathy (PDR).Methods:A cross-sectional study was conducted.Thirty-eight patients (48 eyes) with PDR were enrolled in Henan Eye Hospital from October 2019 to February 2021, including 22 males (28 eyes) and 16 females (20 eyes). The average age of the patients was (51.08±13.35) years.All patients underwent ultra-widefield imaging (UWFI), fundus fluorescein angiography (FFA), optical coherence tomography angiography (OCTA), en face optical coherence tomography (OCT), near-infrared fundus imaging (IR) combined with spectral domain OCT (SD-OCT). Wide field swept-source OCTA (WF-SS-OCTA) was performed in the patients who were unsuitable for FFA.The time required for each examination in one eye and the detection rate of neovascularization at the optic disc (NVD) and retinal neovascularization elsewhere (NVE) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by Henan Eye Hospital (No.HNEECKY-2021[22]). All patients were informed about the method and purpose of the study and voluntarily signed the informed consent form.Results:The mean monocular examination time costs of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA and WF-SS-OCT was (0.51±0.13), (2.08±0.57), (5.79±0.68), (17.66±1.83) and (13.38±1.23)min, respectively.There was a significant overall difference in the mean monocular examination time among the five methods ( F=2 077.960, P<0.001). The detection rates of UWFI, IR+ SD-OCT, OCTA+ en face OCT, FFA+ WF-SS-OCT for NVE and NVD were 52.1%(25/48) and 12.5%(6/48), 81.3%(39/48) and 20.8%(10/48), 83.3%(40/48) and 27.1%(13/48), 93.8%(45/48) and 29.2%(14/48), respectively.There were significant differences in the detection rates of NVE ( χ2=26.460, P<0.001) but not in the detection rates of NVD ( χ2=4.645, P=0.200) among the various methods.Five neovascular buds were detected by OCTA in 3 eyes, but not by FFA. Conclusions:UWFI and IR+ SD-OCT are faster and non-invasive methods for the screening of NVD and NVE in PDR eyes.Compared with FFA, OCTA and en face OCT can show the shape of neovascularization more clearly.FFA provides a wide-range retinal image, but it is time-consuming and invasive.WF-SS-OCTA extends the examination range of OCTA and detects neovascularization non-invasively and faster than FFA.

Analysis of choroidal vascularity index distribution and influencing factors in normal children / 中华实验眼科杂志

Objective:To evaluate the distribution characteristics of choroidal vascularity index (CVI) in macula among normal children using swept-source optical coherence tomography (SS-OCT), and to investigate the influencing factors.Methods:A cross-sectional study was conducted.Sixty-three children aged 6 to 12 years were enrolled in The First Affiliated Hospital of Zhengzhou University from May 2021 to November 2021.Spherical equivalent refraction, axial length (AL) and other ocular biological parameters were measured.Macula-centered CVI and choroidal thickness (ChT) were measured by SS-OCT angiography.According to the ETDRS partition, the obtained image was divided into macular central fovea (0-1 mm diameter), inner ring (1-3 mm diameter) and outer ring (3-6 mm diameter) zones.Data from the right eye were selected for statistical analysis.CVI in the three rings and four zones (superior, temporal, inferior and nasal zones) of the inner and outer rings were compared.Univariate and multiple linear regression analyses were used to analyze the correlation between CVI and sex, AL, anterior chamber depth (ACD), ChT and pupil diameter.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2021-KY-0399-003). Written informed consent was obtained from each guardian.Results:The average CVI in the macular central fovea, inner ring and outer ring were 0.35±0.12, 0.32±0.10 and 0.27±0.08, respectively, with a significant difference ( F=10.96, P<0.001), and significant differences in CVI were found in pairwise comparisons of the three ring zones (all at P<0.05). Significant differences in CVI were found among superior, temporal, inferior and nasal zones in inner and outer rings ( Fring=11.60, P=0.001; Fzone=12.02, P<0.05). The CVI was smaller in superior and nasal zones in inner ring than in temporal zone, greater in superior, temporal and inferior zones in outer ring than in nasal zone, smaller in superior zone of outer ring than that of the inner ring, and the differences were statistically significant (all at P<0.001). The single factor linear regression analysis showed that ChT in the fovea, inner ring and outer ring were the influencing factors of CVI in the three ring zones (all at β=0.001, P<0.001). Pupil diameter ( β=0.034, P=0.038; β=0.040, P=0.003; β=0.024, P=0.011) and ACD ( β=0.097, P=0.034; β=0.097, P=0.013; β=0.061, P=0.032) were the influencing factors of CVI in fovea, inner ring and outer ring.After multiple linear regression analysis, the regression equations were established as follows: CVI in the macular fovea=0.001×ChT in the macular fovea + 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.301 ( R2=0.514, F=6.875, P<0.001); CVI in the inner ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring+ 0.088×AL-0.307 ( R2=0.603, F=9.870, P<0.001); CVI in the outer ring=0.001×ChT in the macular fovea+ 0.001×ChT in the inner ring+ 0.001×ChT in the outer ring-0.135 ( R2=0.601, F=9.781, P<0.001). Conclusions:In children aged 6-12 years old, the CVI is higher in the macular central fovea than in inner and outer rings, and the CVI in nasal zone is the smallest in both inner and outer rings.The thicker the ChT, the higher the CVI in all zones in the macular area; the deeper the anterior chamber, the higher the CVI in the inner ring.

Pure single-port lumpectomy non-lipolysis breast-conserving surgery in the treatment of early-stage breast cancer / 中华内分泌外科杂志

Objective:To summarize the clinical data and experience of pure single-port lumpectomy non-lipolysis breast-conserving surgery (PSLN-BCS) in patients with early-stage breast cancer.Methods:A retrospective analysis was conducted on 400 patients who underwent breast-conserving surgery for early-stage breast cancer in the Second Department of Breast Surgery at Harbin Medical University Cancer Hospital from Jan. 2022 to Jan. 2023. Patients were divided into two groups: PSLN-BCS group ( n=200) and conventional breast-conserving surgery (C-BCS) group ( n=200). The surgical time, intraoperative blood loss, postoperative drainage within three days, and short-term (3 months to 6 months after surgery) complications, including the incidence of residual fluid after drain removal and incision infection were observed. Long-term (6 months after surgery) complications, including the incidence of skin and pectoralis major muscle adhesions in the surgical area and cosmetic results after breast-conserving surgery, were also evaluated. Statistical analysis was performed using R language, and quantitative data were expressed as mean ± standard deviation ( ± s) and analyzed using t-test, while count data were analyzed using χ2 test. A p-value less than 0.05 was considered statistically significant. Results:PSLN-BCS had a longer average surgical time than C-BCS (198.341min vs 62.961min, P<0.001, 95% CI:132.028 vs 138.732). PSLN-BCS had less intraoperative bleeding (18.824 ml vs 22.627 ml, P=0.003, 95% CI: -6.294 vs -1.311) and lower postoperative drainage volume (346.157 ml vs 406.191 ml, P<0.001, 95% CI: -70.571-a-49.496). There were no significant differences in short-term postoperative complications such as subcutaneous fluid accumulation ( χ2=2.33, P=0.127) or incisional infection ( χ2=0.14, P=0.708) between the two groups. The incidence of skin and muscle adhesions in the surgical area was lower in patients who underwent PSLN-BCS at 6 months postoperatively ( χ2=11.58, P<0.001). Patients who received PSLN-BCS achieved better cosmetic outcomes, with a statistically significant difference ( χ2=273.00, P<0.001) compared to those who received C-BCS. Conclusion:Pure single-port lumpectomy non-lipolysis breast-conserving surgery is a safe and effective treatment option for early-stage breast cancer and can be considered as a surgical option for patients with cosmetic requirements.

Evaluation of clinical efficacy and prognostic factors in multiple myeloma patients treated with auto-HSCT: A single-center real-world study / 西安交通大学学报(医学版)

【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.

Is subfibular ossicle excision necessary in the modified Brostr?m procedure for chronic lateral ankle instability? / 中华创伤骨科杂志

Objective:To investigate the effect of subfibular ossicle excision on the clinical efficacy of Brostr?m procedure for chronic lateral ankle instability (CLAI).Methods:From March 2014 to December 2018, 76 patients were treated by the modified Brostr?m procedure using the suture anchor technique for CLAI at Department of Foot & Ankle Surgery, Wuhan Fourth Hospital. Of them, 33 had subfibular ossicles (SFO group) and 43 did not (NSFO group). In the SFO group, there were 19 males and 14 females, aged (28.4±8.6) years; in the NSFO group, there were 21 males and 22 females, aged (27.8±7.4) years. Subfibular ossicles were excised in the SFO group. The 2 groups were compared in terms of American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and visual analogue scale (VAS) pain scores at preoperation and the final follow-up.Results:The 2 groups were comparable due to insignificant differences between them in their preoperative general data ( P>0.05). All the patients were followed up for 24 to 72 months (average, 28 months). The AOFAS ankle-hindfoot scores improved significantly from 54.5±3.4 to 95.7±2.1 in the SFO group and significantly from 56.2±2.7 to 95.2±2.4 in the NSFO group at the final follow-up; the VAS scores reduced significantly from 5.7±1.8 to 1.6±1.4 in the SFO group and significantly from 5.7±1.6 to 1.7±1.2 in the NSFO group at the final follow-up (all P<0.05). No significant differences were found between the 2 groups in terms of AOFAS or VAS scores at the final follow-up ( P>0.05). Conclusion:Since the modified Brostr?m procedure plus subfibular ossicle excision may result in similar good clinical efficacy as merely the modified Brostr?m procedure may for the CLAI patients without subfibular ossicle, subfibular ossicle excision should be suggested for the CLAI patients with subfibular ossicle.

Application effect analysis of artificial intelligence automatic diagnosis system for diabetic retinopathy in elderly diabetic patients in community and hospital / 中华眼底病杂志

Objective:To study the efficiency and difference of the artificial intelligence (AI) system based on fundus-reading in community and hospital scenarios in screening/diagnosing diabetic retinopathy (DR) among aged population, and further evaluate its application value.Methods:A combination of retrospective and prospective study. The clinical data of 1 608 elderly patients with diabetes were continuously treated in Henan Eye Hospital & Henan Eye Institute from July 2018 to March 2021, were collected. Among them, there were 659 males and 949 females; median age was 64 years old. From December 2018 to April 2019, 496 elderly diabetes patients were prospectively recruited in the community. Among them, there were 202 males and 294 female; median age was 62 years old. An ophthalmologist or a trained endocrinologist performed a non-mydriatic fundus color photographic examination in both eyes, and a 45° frontal radiograph was taken with the central fovea as the central posterior pole. The AI system was developed based on the deep learning YOLO source code, AI system based on the deep learning algorithm was applied in final diagnosis reporting by the"AI+manual-check" method. The diagnosis of DR were classified into 0-4 stage. The 2-4 stage patients were classified into referral DR group.Results:A total of 1 989 cases (94.5%, 1 989/2 104) were read by AI, of which 437 (88.1%, 437/496) and 1 552 (96.5%, 1 552/1 608) from the community and hospital, respectively. The reading rate of AI films from community sources was lower than that from hospital sources, and the difference was statistically significant ( χ2=51.612, P<0.001). The main reasons for poor image quality in the community were small pupil (47.1%, 24/51), cataract (19.6%, 10/51), and cataract combined with small pupil (21.6%, 11/51). The total negative rate of DR was 62.4% (1 241/1 989); among them, the community and hospital sources were 84.2% and 56.3%, respectively, and the AI diagnosis negative rate of community source was higher than that of hospital, and the difference was statistically significant ( χ2=113.108, P<0.001). AI diagnosis required referral to DR 20.2% (401/1 989). Among them, community and hospital sources were 6.4% and 24.0%, respectively. The rate of referral for DR for AI diagnosis from community sources was lower than that of hospitals, and the difference was statistically significant ( χ2=65.655, P<0.001). There was a statistically significant difference in the composition ratio of patients with different stages of DR diagnosed by AI from different sources ( χ2=13.435, P=0.001). Among them, community-derived patients were mainly DR without referral (52.2%, 36/69); hospital-derived patients were mainly DR requiring referral (54.9%, 373/679), and the detection rate of treated DR was higher (14.3%). The first rank of the order of the fundus lesions number automatically identified by AI was drusen (68.4%) and intraretinal hemorrhage (48.5%) in the communities and hospitals respectively. Conclusions:It is more suitable for early and negative DR screening for its high non-referral DR detection rate in the community. Whilst referral DR were mainly found in hospital scenario.

Skin fibroblasts derived from Leber's hereditary optic neuropathy patients present mitochondrial dysfunction / 中华眼底病杂志

Objective:To investigate the feasibility of immoribund skin fibroblast cell line derived from Leber's hereditary optic neuropathy (LHON) patients as a cell model.Methods:A basic research. Two LHON patients and 2 healthy volunteers were recruited from Department of Ophthalmology of Genetic Clinic of Henan Provincial Eye Hospital. The skin tissue of participants was obtained, and the 4 immortalized skin fibroblasts were constructed by SV40 virus infection, including 2 LHON patient cells (LHON-1 and LHON-2 cells) and 2 healthy volunteers cells (NC-1 and NC-2 cells). Mitochondrial morphology in cells was observed by electron microscope. The levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide-oxidation state (NAD +), nicotinamide adenine dinucleotide-reduction state (NADH) and adenosine triphosphate (ATP) in fibroblasts were detected. Cellular oxygen consumption was measured by seahorse mitochondrial pressure assay. Cell viability was detected using cell counting kit-8 (CCK8). One-way ANOVA was performed to compare the levels of ROS, NAD +, NADH and ATP in LHON and NC cells, as well as basal oxygen consumption, maximal oxygen consumption, ATP-coupled oxygen consumption, and cell viability. Results:Compared with NC-1 and NC-2, the number of mitochondrial crest in LHON fibroblasts was significantly reduced, indicating abnormal mitochondrial morphology. Biochemical analysis showed that ROS levels in LHON cells increased, but NAD +/NADH and ATP levels decreased, and the oxygen consumption was significantly inhibited, indicating the presence of mitochondrial damage and respiratory dysfunction. The results of CCK-8 detection showed that the survival ability of LHON-1 and LHON-2 cells was worse under stress conditions. Conclusion:Immortalized skin fibroblast cell lines from LHON patients presented mitochondrial dysfunction.

Genotypes and phenotypes analysis of a novel complex heterozygous mutation of CEP290 related isolated cone-rod dystrophy / 中华眼底病杂志

Objective:The clinical phenotypes and pathogenicity of isolated cone-rod dystrophy (CORD) caused by two novel complex heterozygous variants of the CEP290 gene were analyzed using high-resolution multi-mode imaging and gene detection techniques. Methods:A retrospective study. Two patients and two family members from a CORD family who were diagnosed by genetic testing at Henan Provincial People's Hospital in December 2021 were included in the study. All subjects underwent best-corrected visual acuity (BCVA), color fundus photography, autofluorescence, swept-source optical coherence tomography (SS-OCT), adaptive optics fundus imaging, static threshold field, full field and multiple electroretinogram (ERG) examination, as well as other systemic examinations throughout the body. The peripheral venous blood of the subjects was collected, and the whole genome DNA was extracted. DNA sequencing was performed using the Inherited Retinal Disease Kit PS400, and Sanger verification and pedigree co-segregation analysis were performed on the suspected pathogenic mutation sites. Validation was performed by Sanger sequencing, pathogenicity analysis was performed in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Conservation of variation among different species was analyzed by GERP++, Clustal Omega and Weblogo.Results:Both patients were male, and their ages were 21 and 29 years old, respectively. The right eye and left eye about BCVAs were 0.7, 0.4 and 0.3, 0.4, respectively. The full field and multiple electroretinogram ERG showed a decreased function of cones and rods, especially cones. SS-OCT showed thinning of the outer nuclear layer of macular, and attenuation of ellipsoid zone reflectivity in B-scan. Adaptive optics fundus imaging examination showed that the arrangement of cone cells in the fovea of the fovea was disordered and the density decreased, and the retinal pigment epithelial cells were seen through the atrophy of cone cells in some areas at 10°visual angle. No obvious abnormality was found in other systemic examinations of the whole body. Genetic testing showed that 2 novel compound heterozygous variants c.950T >A (p.Leu317*) (M1) and c.4144_4149del (p.Tyr1382_Glu1383del) (M2) in CEP290 were found in two patients. The first variant was predicted to be harmful in MutationTaster and CADD. GERP++ showed highly conserved among different species. The pathogenicity of the variant was suspected to be likely pathogenic according to ACMG guidelines. The pathogenicity of the second variant was uncertain significance. The parents of the proband had no similar ocular abnormalities. Verified by Sanger sequencing, it was consistent with co-separation in the family. Conclusions:Patients with pure CORD caused by CEP290 gene mutation still retain better vision when the cone structure is abnormal, the density is decreased, and the function of cone and rod cells is decreased. CEP290 M1 and M2 are newly discovered nonsense mutations and newly discovered deletion mutations, which expanded the causative gene spectrum of pure CORD.

Research hot spots of ophthalmology-related coronavirus disease 2019 / 中华眼底病杂志

Objective:To study the research hot spots of ophthalmology-related coronavirus disease 2019 (COVID-19).Methods:PubMed database as the data source, the literatures of ophthalmology-related COVID-19 published on January 1, 2020 to February 22, 2022 were collected, limited to Medline included, the language type was limited to English and Chinese, and 1 592 literatures were included. By reading the titles and abstracts, the literatures of meeting notice, editor's note, etc. and the literature that was not quite relevant with ophthalmology-related COVID-19 were removed, and finally 1 547 literatures were included. Bibliographic Items Co-occurrence Matrix Builder (BICOMB 2.02 software) was used to collect the frequency of major Mesh terms/subheadings and the frequency of major Mesh terms after removing the subheadings, and the number of included articles published in the top 10 journals by the number of ophthalmology-related COVID-19 articles was recorded. VosViewer 1.6.18 software was used for cluster analysis of collaborator network and major Mesh terms, and the publication status and country or region distribution of active authors of ophthalmology-related COVID-19 were recorded.Results:Of the 1 547 literatures, the active authors were mainly from India, Italy, Singapore, Spain, and Hong Kong, China, and so on; the top 10 journals published 617 articles in total (39.88%, 617/1 547). The high frequency major Mesh terms/subheadings included COVID-19, viral pneumonia, coronavirus infection, eye diseases/epidemiology, complications, prevention & control, diagnosis, virology, and Severe acute respiratory syndrome coronavirus 2, betacoronavirus/isolation & purification, ophthalmology/education, organization & administration, telemedicine, delivery of health care/organization & administration, and mucormycosis/diagnosis, etc. After taking out the subheadings, the high frequency of major Mesh terms also included conjunctivitis, orbital disease, retinal diseases, neuromyelitis optica, retinal vein occlusion, myopia and other eye diseases, eye diseases-related systemic diseases, such as multiple sclerosis and Miller Fisher syndrome, therapy and prevention-related drugs, such as hydroxyl chloroquine, angiogenesis inhibitors, and vaccination.Conclusions:Ophthalmology-related COVID-19 researches have received extensive attention worldwide, COVID-19 is associated with multiple ocular diseases of anterior and posterior segments. COVID-19-related mucormycosis, hydroxychloroquine and possible retinal toxicity, and possible ocular adverse effects associated with vaccination are also noteworthy.

Practice and exploration of discipline construction in tertiary specialized hospital with a view of high quality development / 中华医学科研管理杂志

Objective:This paper analyzes the factors influencing the development of discipline construction in a tertiary specialized hospital, explores discipline improvement measures, so as to provide possible references for other medical institutions.Methods:Taking Henan Eye Hospital as an example, we analyze the current status of discipline construction, review the managing practice for the development in recent years, find out the factors influencing the development of disciplines and new challenges, and puts forward improvement measures.Results:The managing practice showed that the affecting factors of discipline construction included discipline orientation, talent teams, original innovation, medical level, academic exchanges and research platforms. Facing to the new problems under the further goal, to figure out the novel way is a guarantee for the smooth development of the medical institute.Conclusions:These measures may foster the development of discipline construction, which include focusing on discipline direction, strengthening the construction of talents, encouraging scientific and technological innovation, developing medical services, deepening the domestic and international cooperation and exchange and constructing platforms. It is important to achieve high-quality development of high-level specialized medical institutions for reaching the goal of health for all citizens.

Novel compound heterozygous mutations in the PCDH15 gene in a family affected with Usher syndrome type 1F with retinitis pigmentosa sine pigmento / 中华眼底病杂志

Objective:To identify the causative gene in a family affected with Usher syndrome (USH) with retinitis pigmentosa sine pigmento (RPSP) and to analyze the genotype-phenotype correlation.Methods:A retrospective clinical study. A 9-year-old girl with RPSP type 1F USH diagnosed in the ophthalmology clinic of Henan Provincial People's Hospital in November 2019 and her parents were included in the study. The patient had bilateral night blindness for more than 4 years, she suffered from hearing loss 7 years, and is currently binaural sensorineural deafness. The best corrected visual acuity in both eyes was 0.5 +. There was showed no obvious pigmentation on the fundus. The visual acuity of the peripheral field of vision decreased. Optical coherence tomography showed that the outer layer of the peripheral retina became thinner and the ellipsoid band disappeared. On electroretinogram examination, the rod and cone system response was severely decreased. The clinical phenotype of the parents of the child were normal. The peripheral venous blood of the child and his parents were extracted, the whole genome DNA was extracted, the custom developed targeted capture kit (PS400) was used, and the next-generation sequencing technology was used to detect genetic mutations. The suspected pathogenic mutation sites were verified by Sanger; co-segregation was performed among family members. The pathogenicity of variants were evaluated according to the interpretation standards and guidelines of sequence variants. Bioinformatics techniques were used to assess the impact of variants on encoded proteins. Results:The results of genetic testing showed that the proband detected the PCDH15 gene c.4109dupA (p.K1370fs) (M1), c.17dupA (p.Y6_L7delinsX) (M2) compound heterozygous mutation sites, verified by Sanger sequencing, the mutations were in the family in a state of co-segregation. According to the evaluation of sequence variation interpretation standards and guidelines, M1 and M2 were pathogenic variants of the PCDH15 gene. M1 led to a complete change in the transmembrane structure of the encoded protein, and M2 caused the gene to only translate 6 amino acids, which predicted that the PCDH15 protein cannot be synthesized. According to the clinical phenotype, gene mutation pathogenicity and protein structure prediction, the final clinical diagnosis was PCDH15-related type 1F. Conclusions:PCDH15 genes c.4109dupA and c.17dupA are the pathogenic mutation sites of USH in this family. These compound heterozygous new mutations lead to the failure of normal synthesis of PCDH15 protein, which leads to ocular and ear manifestations.

Genotypic and phenotypic analysis of RHO gene variants in a Chinese Han autosomal dominant retinitis pigmentosa family / 中华实验眼科杂志

Objective:To analyze the pathogenic genes and clinical phenotypes of a Chinese Han family with autosomal dominant retinitis pigmentosa (ADRP).Methods:A pedigree investigation study was conducted, and a Chinese Han RP family that underwent genetic counseling in the Henan Provincial People's Hospital in November 2019 was collected.Twenty members of this family from 4 generations, including 9 patients and 11 phenotypically normal individuals, were enrolled.Visual acuity, peripheral visual field test and fundus examination were performed on some family members.Peripheral blood samples were collected from the family members, and DNA was extracted.Exon-targeted sequencing containing 43 genes associated with RP was performed on the proband using the Ion Torrent PGM sequencing platform.The mutations were verified by polymerase chain reaction and Sanger sequencing.Online software was applied to predict the protein function of the variant.The amino acid sequences of the variant loci were compared using the ClustalW2 multiplex alignment program.The pathogenicity of the variant was analyzed according to American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variant.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2019[15]).Results:The family was consistent with autosomal dominant inheritance.The proband, a 26-year-old male, had bilateral night blindness since childhood, with visual acuity of 0.25 in the right eye and 0.5 in the left eye.There was osteoblast-like pigmentation in his both retinas, thinned retinal vessels and pale optic disc.Full-field electroretinogram examination showed reduced scotopic a- and b-wave peaks and severely reduced photopic a- and b-wave peaks.The rest of the family began to develop night blindness when 7 to 10 years old, having complete loss of peripheral vision around 50 years of age, and typical RP changes were found in ophthalmic examination.Genetic testing revealed a heterozygous missense variant c. 982delC (p.L328fs) in exon 5 of the family's rhodopsin ( RHO) gene (NM_000539.3). This variant resulted in the change of 21 amino acids after amino acid 328 in the encoded RHO protein, increasing amino acids in the coding region from 348 to 358 and altering the structure of the RHO protein.The analysis of protein homology sequence alignment between several different species showed that the locus was highly conserved.According to the guidelines of the ACMG criteria and guidelines for classification of genetic variants, the variant was a pathogenic mutation because there were six evidences including one very strong evidence of pathogenicity PVS1, two moderate evidences of pathogenicity PM2 and three supporting evidences of pathogenicity, PP1, PP3 and PP4. Conclusions:The c. 982delC variant in the RHO gene is a pathogenic mutation in this pedigree, and this variant is reported for the first time in a Chinese Han family.

Quantitative analysis of the measurements in retinal capillary nonperfusion areas in proliferative diabetic retinopathy patients / 中华眼底病杂志

Objective:To compare the quantitative measurements of the retinal capillary nonperfusion areas in a cohort of proliferative diabetic retinopathy (PDR) patients with fluorescein fundus angiography (FFA) and swept source optical coherence tomography angiography (SS-OCTA), and to determine the intrapersonal variability between examiners.Methods:A cross-sectional study. Eighteen eyes of eleven PDR patients diagnosed in Department of ophthalmology of Henan Provincial People's Hospital from September 2019 to January 2020 were included in this study. FFA was performed using Spectralis HRA+OCT (Germany Heidelberg Company) from and SS-OCTA was performed using VG200D (China Vision Micro Image Corporation). SS-OCTA was used to collect images of retinal layer, superficial capillary plexus (SCP) and deep capillary plexus (DCP). The same observation area was 80°×60° for SS-OCTA and 55° for FFA with both setting centered on the fovea. The forty-nine retinal capillary nonperfusion areas were observed. The area measurement was completed independently by three examiners. Paired sample t test or paired sample Wilcoxon test were used to compare the measured values of retinal capillary nonperfusion areas between the two examination methods and among the three examiners. Results:There was no significant difference in the retinal layer, SCP and DCP nonperfusion area measured by FFA and SS-OCTA among the three examiners ( P>0.05), and the consistency is good (consistency correlation coefficient> 0.9, P<0.05). The nonperfusion area measured by FFA was 0.786 mm 2. The median nonperfusion area of retinal layer and SCP measured by SS-OCTA were 0.787 mm 2 and 0.791 mm 2, respectively, and the average nonperfusion area of DCP was 0.878±0.366 mm 2. The nonperfusion area of retinal layer and SCP measured by FFA and SS-OCTA showed no statistically significant difference ( P=0.054, 0.198). The nonperfusion area of DCP measured by SS-OCTA was significantly larger than that of FFA, and the difference was statistically significant ( P<0.001). The results of repeatability analysis showed that 93.88% (46/49) of the DCP nonperfusion area data measured by SS-OCTA were greater than those measured by FFA. Conclusion:The retinal nonperfusion area of DCP in PDR patients measured by SS-OCTA is larger than that of FFA.

A novel mutation of CNGB3 gene in a Chinese achromatopsia family / 中华实验眼科杂志

Objective:To identify the pathogenic gene mutations in a Chinese achromatopsia family.Methods:A pedigree investigation was performed.A Chinese Han pedigree from Luoyang city of China was enrolled in Henan Eye Hospital in November 2018.The medical history of the patients was collected.The best corrected visual acuity (BCVA) of the families was examined.The maniafestations of the anterior segment and fundus were obtained via slit lamp biomicroscope and slit lamp lens.The diopter was determined by objective and subjective refraction.Color vision was examined by Farnsworth-Munsell Hue Test.Retinal function was evaluated by international standard electroretinogram (ERG). Retina was observed by color photography, and its structural image was obtained by spectral-domain optical coherence tomography (SD-OCT). The peripheral blood sample was collected from the proband (Ⅲ1) and her younger brother (Ⅲ2) and parents for whole blood DNA extraction, and a whole genome sequencing (WGS) was performed to identify the pathogenic genes and mutation sites, and the sequencing data was compared through disease-related databases such as the Human Genome Databases due to a negative detective result of specific hereditary eye disease enrichment panel based on targeted exome capture technology.Sanger sequencing and bioinformatics analysis was carried out with softwares.The cosegregation analysis was performed.This study protocol was approved by an Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]) and complied with Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian before any medical examination.Results:This family included 2 patients and 8 members with normal phenotypes in 3 generations and showed an autosomal recessive inheritance model.Poor vision and photophobia appeared after birth in both Ⅲ1 and Ⅲ2, and these symptoms did not deteriorate with aging.Pigmentary mottling and atrophic changes could be seen in the retinas of the patients.Reflection bands of external membrane and ellipsoid line in macula of patients were irregular on the OCT image.Color vision examination showed achromatopsia of the patients.ERG indicated that the amplitudes of a-, b-waves of scotopic 0.01, 3.0, 10.0 ERG and oscillatory potentials were slightly reduced, and the amplitudes of a-, b-waves of photopic ERG and wavelets of 30 Hz were seriously reduced in both eyes of Ⅲ1 and Ⅲ2.WGS showed that heterozygous mutations of a novel mutation c. 129+ 1G>A and a known mutation c. 1285dupT of CNGB3 gene in Ⅲ1 and Ⅲ2.The mutations were confirmed by Sanger sequencing.Conclusions:The compound heterozygous mutation in c. 129+ 1G>A/c.1285dupT of CNGB3 gene may be responsible for the achromatopsia pathogenesis in this Chinese Han pedigree.The abnormal phenotype of the patients is the result of both CNGB3 c. 129+ 1G>A and CNGB3 c. 1285dupT mutations simultaneously.

3D printed individualized osteotomy template for treatment of painful talocalcaneal coalition of Rozansky types Ⅲ-Ⅳ / 中华创伤骨科杂志

Objective:To explore the effectiveness of 3D printed individualized osteotomy template for the treatment of painful talocalcaneal coalition of Rozansky types Ⅲ-Ⅳ.Methods:From January 2016 to August 2018, a 3D printed individualized osteotomy template was used in 14 patients with painful talocalcaneal coalition at Department of Foot and Ankle Surgery, Wuhan Fourth Hospital. They were 8 males and 6 females, aged from 19 to 42 years (mean, 30.2 years). CT scan of full bilateral feet was conducted. The bone bridge to be resected was marked and an individualized template designed taking the CT scans of the healthy foot as mirror images. The 3D individualized templates were used to assist resection of talocalcaneal coalitions. Scores of visual analogue scale(VAS) and American Orthopaedic Foot and Ankle Society (AOFAS) and complications were recorded at the final follow-up.Results:The 14 patients obtained an average follow-up of 21.6 months. Their VAS and AOFAS ankle and hindfoot scores (2.3±0.7 and 86.5±4.5) at the final follow-up were significantly improved compared with their preoperative values (7.0±1.9 and 37.1±6.0) ( P<0.05). Their follow-up X-ray films showed no recurrence of talocalcaneal coalition or traumatic arthritis. Conclusion:A 3D printed individualized osteotomy template is an effective assistance in the treatment of talocalcaneal coalition because it can lead to accurate location of the talocalcaneal bridge and full osteotomy.

Emergent foot and ankle surgery in the epidemic of COVID-19 / 中华创伤骨科杂志

Objective:To report our experience in the emergent foot and ankle surgery in the epidemic of COVID-19.Methods:The data of 18 patients with acute foot and ankle injury were reviewed who had been admitted to the Department of Foot and Ankle Surgery, Wuhan Fourth Hospital from 20th January, 2020 to 26th February, 2020. They were 11 men and 7 women, aged from 18 to 70 years (average, 42.5 years). There were 5 cases of acute open injury and 13 ones of acute closed injury. COVID-19 infection was diagnosed or suspected in 5 cases but not in the other 13 cases. Emergency operation was carried out for 2 patients with open injury plus COVID-19 infection and one with complicated pilon fracture plus COVID-19 infection, one of whom received secondary operation. One patient with closed fracture of the left calcaneus plus COVID-19 infection was hospitalized from emergency department for secondary surgery, and another with closed fracture of the right lateral malleolus was referred to the isolation ward after emergency plaster fixation. Of the 10 patients with closed injury but without COVID-19 infection, 3 received conventional secondary surgery after admission and the others conservative treatment at the outpatient department. Recorded were COVID-19 infections in the patients after admission and in the medical staff. The measures taken and experience in control and prevention of COVID-19 infection after outbreak of the epidemic were reviewed.Results:Of the 11 patients who had been hospitalized for foot and ankle injury in emergency, 5 were definitely diagnosed of or suspected of COVID-19 infection and 6 free of COVID-19 infection. During hospitalization, COVID-19 infection was confirmed in the 5 cases and no COVID-19 infection occurred in the other 6 patients. No COVID-19 infection occurred in the medical staff; no cross infection was observed between the patients and the medical staff.Conclusions:Reasonable strategies are advised to balance the foot and ankle surgery and epidemic prevention. A simplified management is not advised for all the cases. The operative procedures in emergent foot and ankle surgery should be optimized in line with the epidemic control and prevention principles to facilitate functional rehabilitation for the patients.

Anatomical reconstruction of the lateral ankle ligament with an individualized 3D printed drill template / 中华创伤骨科杂志

Objective:To evaluate the clinical application of an individualized 3D printed drill template to create a fibular channel in the anatomical reconstruction of the lateral ankle ligament for chronic lateral ankle instability.Methods:From October 2012 to June 2015, 15 patients with lateral ankle in-stability underwent surgery at Department of Foot and Ankle Surgery, The Fourth Hospital of Wuhan.They were 4 men and 11 women, with a mean age of 26.3 years (range, from 18 to 42 years).For each of them, anatomical reconstruction of the lateral ankle ligament was performed through a fibular channel which was created with the aid of an individualized 3D printed drill template.The American Orthopaedic Foot and Ankle Society (AOFAS) and Visual Analogue Scale (VAS) scores were used to assess the patients preoperation and at the last follow-up.Results:The 15 patients obtained a mean follow-up of 15.2 months (range, from 12 to 18 months).Their preoperative AOFAS scores (47.1±3.8) were increased to 88.3±4.7 at the last fol-low-up, and their preoperative VAS scores (5.8±1.8) decreased to 1.55±1.35 at the last follow-up, showing significant differences ( P<0.05).There were 11 excellent and 4 good cases by the AOFAS ankle-hindfoot scale.No significant complications were found. Conclusion:In the anatomical reconstruction of the lateral ankle ligament for chronic lateral ankle instability, an individualized 3D printed drill template can help create a fibular channel which exactly fits each individual, leading to positive therapeutic effects.

X linked rod-cone dystrophy associated with a novel splicing variation in the intron of OPN1LW gene / 中华实验眼科杂志

Objective:Mutations in the OPN1LW gene located in X chromosome usually lead to blue cone monochromacy.Variations in OPN1LW gene usually occur in the exon region, but was rare in the intron region.This study was to report a Chinese family with X-linked rod-cone dystrophy associated with a novel OPN1LW gene hemizygotic splicing variation and analyze the clinical phenotype and gene mutation characteristics Methods:A pedigree investigation was performed.The family members clinically diagnosed as rod-cone dystrophy with myopia were enrolled in Henan Provincial People's Hospital on January 9, 2020.Detailed ophthalmological examination was carried out, and the periphery venous blood was collected for DNA extraction.The target gene sequencing panel PS400 developed by Henan Clinical Research Center for Eye Diseases and whole exon sequencing were used to detect pathogenic mutations.Sanger sequencing and pedigree co-segregation were used to verify variations.The pathogenicity of the novel variation was analyzed based on American College of Medical Genetics (ACMG) Guidelines and online tools SIFT, Polyphen2, Mutation Taster.This study adhered to the Declaration of Helsinki, and the study protocol was approved by the Medical Ethics Committee of Henan Eye Hospital (HNEECKY-2019 [15]). Written informed consent was obtained from each family member before any medical examination.Results:The proband was a 5-year-old boy with poor vision, red-green blindness and nystagmus in both eyes.No obvious abnormality in ocular anterior segment was found.The boundary of optic disc was clear and the color was reddish, and the reflection of macular fovea was clearly visible.OCT image showed indistinct reflection of some ellipsoids in macular area of both eyes.The amplitudes of a and b waves of full-field ERG were not recorded in scotopic 0.01 scale and significantly reduced in scotopic 3.0 and photopic 3.0 ERG.The uncle of the proband had a more severe clinical phenotype.Wide-angle fundus photography showed high myopia findings, peripheral retinal atrophy and sporadic black lesions, and autofluorescence examination showed attenuated fluorescence in peripheral retina.No obvious abnormality was found in the middle-peripheral retinal region.The results of two kinds next generation sequencing showed a novel hemizygotic splicing variation c. 112+ 2T>G in the intron of OPN1LW gene and an unreported heterozygous variation c. 1913A>C (p.Y638S) in the SEMA4A gene.The c. 112+ 2T>G mutation further leaded to the sequence change of classic splice donor of intron 1.According to the ACMG guidelines, the pathogenicity score was PVS1+ PM2+ PP1, which was considered as a pathogenic level. Conclusions:This is the first report of X-linked rod-cone dystrophy associated with OPN1LW gene variation, and this novel variant c. 112+ 2T>G locates in the intron region.This result is different from past knowledge that variations of OPN1LW gene primarily occur in exon.This study expands the mutational spectrum of OPN1LW gene inducing retinal degeneration and the spectrum of clinical phenotype.

Analysis of National Natural Science Foundation of China grant support for basic research of ophthalmology during the past ten years / 中华实验眼科杂志

Objective:To review the detail data of National Natural Science Foundation of China (NSFC) grant support during past decade and to analyze the tendency of basic and applied science researches in ophthalmology and vision science.Methods:The detail data of grants supported by NSFC in the field of ophthalmology and vision science during 2010—2019 were collected.The project category, project name, principle investigator, amount of grant, supported institute and region distribution were analyzed.Cluster analysis of key words associated with the projects was performed with VOSviewer software.Results:During the past decade, the number of projects and the total amount of funding from NSFC were stable in ophthalmology and vision science, which accounted for about 2% of medicine field.The number of keywords representing advanced researches, hotspots areas and methodologies increased.Retinal and choroidal diseases, corneal and ocular surface diseases, glaucoma and optic nerve diseases ranked in the top three in the granted projects.Granted projects mainly went to the well-developed areas in economy and education.The high-level talent projects primarily were in the institutes and universities with solid and profound scientific research background.Conclusions:The sustained and stable support of NSFC plays a promoting role in the development of ophthalmology and vision science and talent cultivation.The new technology and its integration with interdisciplinary science promote the development of ophthalmology.Successfully granted projects appear to be related to the regional environment of economy, education and scientific research background.