[Clinical and molecular genetic analysis of Angelman syndrome with oculocutaneous albinism type 2: A case report and literature review].

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.

[Research progress on the pathogenesis of diabetes-related dry eye].

In recent years, with the further understanding of medical circles on diabetic ocular complications, the ocular surface abnormalities of diabetes has drawn increasing concerns. Nearly 50% of diabetic patients suffer from dry eye symptoms. The main manifestations of diabetes related dry eye were abnormal lacrimal secretion, poor lacrimal stability, decreased corneal sensitivity, persistent corneal epithelial defect and even corneal ulcer, which were mainly related to the changes of structure and function of lacrimal gland, the decrease of goblet cells in conjunctiva, the abnormality of meibomian gland function and the degeneration of corneal nerve caused by diabetes. In this paper, we summarized and analyzed the recent research progress on the effect of diabetes on lacrimal film, corneal innervation and lacrimal gland innervation, and the correlation between oxidative stress, advanced glycation end products and diabetes-related dry eye, to explore the pathogenesis of diabetes-related dry eye and to provide reference for clinical diagnosis, treatment and research.

[Research progress of diabetic corneal neuropathy].

Diabetic neuropathy is a common complication of diabetes. Its incidence among diabetic patients is more than 50%, and its ocular manifestations include diabetic retinopathy and diabetic corneal neuropathy. By using confocal microscopy, diabetic neuropathy in the cornea has been found to occur earlier than other parts of the body, which helps for early diagnosis, risk assessment and treatment options for diabetic peripheral neuropathy. The repair and treatment of nerve damage in diabetic corneal neuropathy has been frequently studied. This review focuses on the research progress of diabetic corneal neuropathy in recent years, and discusses the research findings on corneal nerve injury, anatomical and functional changes, and mechanism of injury and repair. (Chin J Ophthalmol, 2021, 57: 630-636).

[Investigation on prevention and treatment status of VTE in pregnant women of general hospitals and specialized hospitals in China].

Objective: To investigate the prevention and treatment status of venous thromboembolism (VTE) of pregnant women in general hospitals and specialized hospitals in China. Methods: This study was a cross-sectional survey about VTE prevention and treatment in 112 hospitals across China from January 1st to December 31st, 2019, including general information, resource accessibility, hospital system and strategy. According to the characteristics, the hospitals were divided into general hospital group (70 hospitals) and specialized hospital group (42 hospitals). The basic information, VTE diagnosis and treatment resources, prevention systems and the preference of the VTE risk assessment form of the two groups were compared. Logistic regression was used to analyze the proportion of VTE incidence and related factors in the two groups of hospitals. Results: (1) The median annual delivery volume of the general hospital group was significantly lower than that of the specialized hospital group (3 428 vs 9 969 cases, P<0.01), the diagnostic accessibility of CT pulmonary angiography (CTPA) was significantly higher than that of the specialized hospital [92.9% (65/70) vs 59.5% (25/42), P<0.01], and the proportion of obstetric VTE risk assessment was significantly higher than that of the specialized hospital group [85.7% (60/70) vs 66.7% (28/42), P=0.017]. (2) Among the 88 hospitals using the VTE risk assessment sheet, the utilization rate of the evaluation sheet recommended by the obstetric VTE guideline in specialized hospitals (78.6%, 22/28) was higher than that of general hospitals (48.3%, 29/60), and the difference was statistically significant (P=0.007). (3) The proportion of VTE incidence in general hospital group was 0.126% (360/286 517), and the proportion of VTE incidence in specialized hospital group was 0.032% (154/484 111). Logistic regression analysis showed that the OR value of the specialized hospital group was 0.253 (95%CI: 0.209-0.305) and the difference was statistically significant (P<0.01) compared with the general hospital group. After adjusting the hospital level, B-ultrasonography and CTPA accessibility, whether to establish a risk assessment and obstetric VTE system, the proportion of VTE incidence in specialized hospitals was still lower than that in general hospitals (OR=0.307, 95%CI: 0.251-0.376, P<0.01). Conclusions: General hospitals have higher access to resources for diagnosing VTE than specialized hospitals, and the VTE evaluation system is better implemented. The utilization rate of the obstetric VTE guidelines in specialized hospitals is higher than that of general hospitals.

[A special on epidemic prevention and control: analysis on expression of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446).

[Strengthening basic and clinical research on ocular infection caused by coronavirus].

This article was published ahead of print on the official website of Chinese Jounal of Ophthalmology on February 19, 2020. The prevention and treatment of coronavirus disease 2019 (COVID-2019) has reached the critical stage in China. Ocular surface represents a possible route for infection. Based on the previous studies and our own research, we summarize the potential transmission route and clinical symptoms of COVID-2019 in the eye, as well as the further prevention and research, with the expectation of contributing to the development in the field of infectious eye disease in China. (Chin J Ophthalmol, 2020, 56:250-252).

[The research progress of relationship between advanced glycation end products and diabetic keratopathy].

Diabetic keratopathy is a common ocular complication of patients with a long-term history of diabetes and it will have a negative effect on the visual quality and function. A study reported that the incidence of diabetic keratopathy in diabetic patients ranged from 47% to 64%, but the precise underlying pathogenesis remains unclear. There is evidence that advanced glycation end products contribute substantially to the onset and progress of various diabetic complications and it is a key factor for the mechanism of the hyperglycemic memory. This review focuses primarily on the present research state and prospect of advanced glycation end products and their role in the pathological changes of the cornea. (Chin J Ophthalmol, 2018, 54: 475-480).