A novel PAX6 variant as the cause of aniridia in a Chinese patient with SRRRD.

BACKGROUND: The genotype characteristics and their associated clinical phenotypes in patients with aniridia were analyzed to explore pathogenic variants using whole-exome sequencing. METHODS: One patient with aniridia was enrolled at the Beijing Tongren Hospital. Comprehensive ophthalmic and general examinations were performed on the patient. DNA was extracted from the patient, and whole-exome sequencing was performed to identify the causative variant. The pathogenicity of the variant was predicted using in silico analysis and evaluated according to American College of Medical Genetics and Genomics guidelines. Relationships between genetic variants and clinical features were analyzed. RESULTS: In addition to the classical aniridia phenotype showing complete iris aplasia, foveal hypoplasia, and ectopic lentis, the patient also exhibited spontaneous reattachment rhegmatogenous retinal detachment (SRRRD). Whole-exome sequencing identified a novel heterozygous variant, exon8:c.640_646del:p.R214Pfs*28. CONCLUSIONS: The present study broadens the range of genetic variants described in aniridia and presents an aniridia patient with SRRRD.

A novel CREBBP mutation and its phenotype in a case of Rubinstein-Taybi syndrome.

BACKGROUND: This study was to report a novel CREBBP mutation and phenotype in a child with Rubinstein-Taybi syndrome. METHODS: Case report of a 9-year-old boy. RESULTS: We described the patient's clinical manifestations in detail, and found that in addition to the typical systemic manifestations of the syndrome, the outstanding manifestation of the child was severe intellectual deficiency and prominent ocular abnormalities. Whole-exome sequencing and sanger sequencing were performed on the patient and his parents, a large intragenic deletion, covering the exon 1 region and part of the intron 1 region of the TRAP1 gene, and the entire region from intron 27 to exon 30 of the CREBBP gene (chr16:3745393-3783894) was identified on the patient. This mutation affected the CREBBP histone acetyltransferase (HAT) domain. CONCLUSIONS: This findings in our patient add to the spectrum of genetic variants described in Rubinstein-Taybi syndrome and present a RSTS patient with various ocular anomalies including early onset glaucoma.

Suprachoroidal hemorrhage associated with pars plana vitrectomy.

PURPOSE: To analyze the characteristics, related risk factors, and prognosis of suprachoroidal hemorrhage (SCH) associated with pars plana vitrectomy (PPV). METHODS: Cases of SCH associated with PPV excluding trauma were retrospectively analyzed in Beijing Tongren Hospital between January 2010 and June 2020. The data collected included general data, myopia status, axial length, state of the crystalline lens, SCH onset time, range, treatment method, visual prognosis, and methods of operation and anesthesia. Patients were divided into those with SCH related to the first PPV (Group 1), and SCH related to second intraocular surgery in the vitrectomized eye (Group 2). Patients were also classified by the SCH onset time into either the expulsive suprachoroidal hemorrhage group (ESCH) and the delayed suprachoroidal hemorrhage group (DSCH). The general data, related risk factors, and the visual prognosis of SCH in the different groups were analyzed. RESULTS: SCH associated with PPV was studied in 28 cases with an incidence of 0.06 %; 16 males and 12 females. The mean age of the patients was (53.51 ± 10.21) years old, the mean follow-up time was (24.94 ± 14.60) days, and the mean axial length was (28.21 ± 3.14) mm. Of these cases, 21 were classified as high myopia, 25 as aphakia/ pseudophakic, and 7 as focal hemorrhage. Silicone oil removal occurred in 12 cases (43 %). Patients in Group 2 were younger than Group 1 (P = 0.005). In terms of treatment and prognosis, 5 eyes were simply closely observed, 4 were given single suprachoroidal drainage, 15 were given suprachoroidal drainage combined with silicone tamponade, 2 underwent anterior chamber puncture, and 2 gave up treatment. A follow-up vision: NLP ~ 20/30; among them, 2 eyes with NLP (7.14 %), 6 of ≥ 20/200 (21.43 %). The final outcomes presented a significantly positive correlation with baseline vision but no significant correlation with age or axial length. CONCLUSIONS: SCH has a higher incidence rate after a second intraocular surgery in a vitrectomized eye which is associated with the lack of vitreous support and easier fluctuation of intraocular pressure. SCH associated with PPV is more localized and has a relatively good prognosis; high myopia and aphakic/ pseudophakic eyes are risk factors. Active treatment can effectively improve visual prognosis. TRIAL REGISTRATION: Retrospective case series study, not applicable.

Peptidome profiling of human serum of uveal melanoma patients based on magnetic bead fractionation and mass spectrometry.

AIM: To find new biomarkers for uveal melanoma (UM) by analyzing the serum peptidome profile. METHODS: Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer were used to compile serum peptide profiles. RESULTS: A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group. Based on combined use of these potential markers, peptides with mean molecular masses of 1467 and 9289.0 Da provide high sensitivity (83.3%), specificity (100%) and accuracy rate (93.0%) together to differentiate melanoma patients from healthy controls. At the time point of 6mo postoperatively, the levels of many peptides differentially expressed before surgery showed no more statistical difference between the patients and the control group. Fibrinogen α-chain precursors were identified as potential UM markers. CONCLUSION: We have shown that a convenient and fast proteomic technique, affinity bead separation and MALDI-TOF analysis combined with bioinformatic software, facilitates the identification of novel biomarkers for UM.

The genetic spectrum of familial hypercholesterolemia in the central south region of China.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common and severe autosomal dominant lipid metabolism dysfunction, which causes xanthoma, atherosclerosis and coronary heart disease. Earlier studies showed that mutations in LDLR, APOB and PCSK9 cause FH. Although more than 75% of the population in Europe has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to perform a survey and mutation detection among the Chinese population. METHODS: 219 FH patients from the central south region of China were enrolled. After extracting DNA from circulating lymphocytes, we used direct DNA sequencing to screen each exon of LDLR, APOB and PCSK9. All detected variants were predicted by Mutationtaster, Polyphen-2 and SIFT to assess their effects. RESULTS: In total, 43 mutations were identified from 158 FH patients. Among them, 11 novel mutations were found, including seven LDLR mutations, two APOB mutations and two PCSK9 mutations. Moreover, five common mutations in LDLR were detected. We geographically marked their distributions on the map of China. CONCLUSIONS: The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Along with future studies, our study provides the necessary data as the foundation for the characterization of the allele frequency distribution in the Chinese population. The identification of more LDLR, APOB and PCSK9 novel mutations may expand the spectrum of FH-causing mutations and contribute to the genetic diagnosis and counseling of FH patients.

Light-mediated control of gene expression in filamentous fungus Trichoderma reesei.

We developed a light-mediated system based on synthetic light-switchable transactivators. The transactivators bind promoter upon blue-light exposure and rapidly initiate transcription of target transgenes in filamentous fungus Trichoderma reesei. Light is inexpensive to apply, easily delivered, and instantly removed, and thus has significant advantages over chemical inducers.

Analysis of post-operative endophthalmitis after pars plana vitrectomy: a 10-year experience at a single center.

BACKGROUND: Endophthalmitis can be a devastating complication after pars plana vitrectomy. The incidence of postvitrectomy endophthalmitis is significantly lower than that of endophthalmitis occurring after other intraocular operations. However, normal post-operative pain and inflammation may mask endophthalmitis and lead to delayed diagnosis and grave visual consequences. This study aimed to summarize the outcomes of cases that underwent pars plana vitrectomy over a 10-year period and to analyze the characteristics of post-vitrectomy endophthalmitis. METHODS: A retrospective observational case study was conducted on all the cases who underwent pars plana vitrectomy in the Beijing Tongren Hospital between January 1, 2002 and March 31, 2012. All cases of endophthalmitis that occurred during a period of 10 years and 3 months were reviewed, and the possible risk factors, clinical findings, causative organism(s), and the sources of infection were analyzed. RESULTS: Within the 10-year observational period, 14 patients developed endophthalmitis after pars plana vitrectomy. The incidence of post-vitrectomy endophthalmitis (0.05%) was lower than that reported previously from the same center (0.12%). Staphylococcus epidermidis (five patients, 35.71%) was the most common organism identified in aqueous or vitreous cultures. Eight patients (57.14%) had diabetes mellitus. There was no statistically significant difference (P > 0.05) in the incidence of endophthalmitis between period 1 (with antibiotic pretreatment) and period 2 (without antibiotic pretreatment). Surgical procedures for the treatment of endophthalmitis were performed in 10 patients (71.43%). CONCLUSIONS: This series of cases showed that the incidence of endophthalmitis after pars plana vitrectomy is lower than what was previously reported in our hospital. A variable degree of corneal edema with relatively normal or mildly increased intraocular pressure was one of the commonly observed characteristics of post-vitrectomy endophthalmitis. Staph. epidermidis was the most common causative organism, and antibiotic pretreatment did not lower the incidence of postvitrectomy endophthalmitis.

Effect of the regimen of Gaoshan Hongjingtian on the mechanism of poly (ADP-ribose) polymerase regulation of nuclear factor kappa B in the experimental diabetic retinopathy.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) plays an important role in the death of retinal capillary cells in diabetic retinopathy (DR) partly via its regulation of nuclear factor kappa B (NF-κB). The current study investigated the effect of the regimen of Gaoshan Hongjingtian (RG) on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian (Rhodiola sachalinensis, RS) on diabetic retinopathy. METHODS: Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 (ICAM-1) in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction (PCR). In addition, the basement membranes of capillaries in the rats' retinas were observed using electron microscopy, and diabetes-induced capillary degeneration (ghost pericytes and acellular capillaries) were quantitated. RESULTS: From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-κB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries (ghost pericytes and acellular capillaries) was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-κB, and ICAM-1 in the retinas of diabetic rats at the end of 5-month diabetic duration. Treatment using RG and RS significantly inhibited increases in the number of acellular capillaries and pericyte ghosts and suppressed the basement membrane thickening in the retinas of rats with diabetes for 8 months compared with the control diabetic rats. CONCLUSIONS: These results indicate that PARP plays an important role in the pathogenesis of diabetic retinopathy. RS and RG may have acted on the mechanism of PARP regulation of NF-κB, which suppressed the expression of NF-κB and ICAM-1, and led to the inhibition of retinal capillary degeneration.

[An investigation on the trend and related determinants of cigarette smoking on experimental smokers among undergraduate students in Changsha].

OBJECTIVE: To investigate the trend and related determinants of cigarette smoking on experimental smokers among undergraduate students in Changsha. METHODS: Stratified sampling method was adopted and 3600 undergraduate students from grade 1 to 3 in Changsha city were investigated through a self-administered questionnaire. All the experimental smokers during the last month were selected and divided into two groups based on the present smoking status. χ(2) test and logistic regression analysis were used to compare the differences of cigarette smoking among subpopulations and to explore the determinants. RESULTS: Among the 1550 experimental smokers of undergraduate students, the prevalence of cigarette smoking was 30.8% (95%CI: 28.5 - 33.1). Students from the second-class (OR = 2.367) or the third-class universities (OR = 2.562) were more likely to adopt smoking behavior than those from top universities. Students majored in sports or arts (OR = 2.456) were significantly more inclined to smoke than the liberal arts students. Students whose father were cadres (OR = 1.602) were more likely to become smokers than those whose fathers were workers. Students being males (OR = 7.386), having high monthly expenses (OR = 1.139), with positive attitude to smoking benefits (OR = 1.140) were risk factors for smoking. Number of smoking members in the family (OR = 1.801) was significantly associated with the prevalence of cigarette smoking. Knowledge on diseases caused by smoking (OR = 0.806) was protecting factor to smoking among the experimental smokers. CONCLUSION: Those experimental smokers among undergraduate students might become smokers and the determinants of cigarette smoking behavior would include: ranking of universities, students' major, gender, father's occupation, amount of pocket money, number of smoking members in the family, knowledge about smoking, the attitude to the benefit of smoking.