De Novo Mutations Contributes Approximately 7% of Pathogenicity in Inherited Eye Diseases.

Purpose: The purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs). Methods: To determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist. Panel-based targeted exome sequencing was performed on DNA extracted from blood samples, containing coding regions of 792 IED-causative genes and their flanking exons. All participants underwent genetic testing. Results: All proband-parent trios were divided into 22 subgroups, the overall diagnostic yield was 48.67% (605/1243), ranging from 4% to 94.44% for each of the subgroups. A total of 108 IED-causative genes were identified, with the top 24 genes explaining 67% of the 605 genetically solved trios. The genetic etiology of 6.76% (84/1243) of the trio was attributed to disease-causative DNMs, and the top 3 subgroups with the highest incidence of DNM were aniridia (n = 40%), Marfan syndrome/ectopia lentis (n = 38.78%), and retinoblastoma (n = 37.04%). The top 10 genes have a diagnostic yield of DNM greater than 3.5% in their subgroups, including PAX6 (40.00%), FBN1 (38.78%), RB1 (37.04%), CRX (10.34%), CHM (9.09%), WFS1 (8.00%), RP1L1 (5.88%), RS1 (5.26%), PCDH15 (4.00%), and ABCA4 (3.51%). Additionally, the incidence of DNM in offspring showed a trend of correlation with paternal age at reproduction, but not statistically significant with paternal (P = 0.154) and maternal (P = 0.959) age at reproduction. Conclusions: Trios-based genetic analysis has high accuracy and validity. Our study helps to quantify the burden of the full spectrum IED caused by each gene, offers novel potential for elucidating etiology, and plays a crucial role in genetic counseling and patient management.

Water search and rescue (SAR) for ship accidents in China: analysis of 12 years' data.

Background: Maritime search and rescue (SAR) remains a great global challenge because of the long distances, harsh environment and complicated trauma. A systematic investigation and analysis of China Maritime Search and Rescue Center (CMSRC) data has been lacking. This study aimed to provide more insightful information for future development of a better maritime and aquatic SAR system in China. Methods: This retrospective study retrieved and analyzed data on the water traffic volume from The Ministry of Transportation, People's Republic of China website and SAR data on ship accidents between January 1, 2008 and December 31, 2019. Spearman's correlation test was performed to analyze the data for the number of ship accidents, number of persons in distress, number of rescued persons, SAR success rate, and SAR forces. The χ2 test was used to assess significant changes in the proportion of ship accident locations, categories, dispatched SAR forces, and location of deaths annually. The Cox Stuart test was applied to determine the trends in the data from 2008 to 2019. Results: Between 2008 and 2019, a total of 24,013 ship accidents were reported and recorded by the CMSRC surveillance system; 209,948 persons in distress because of ship accidents were reported; 8,051 individual deaths from ship accidents. Water traffic volume and ship carrying capacity increased while the annual number of persons in distress, ship collisions, and ship collision-related deaths decreased. The SAR success rate (96.17%±0.92%) did not improve despite an increase in the number of rescue ships dispatched during this period. Helicopters (92.40±20.58 min) arrived faster than rescue ships (283.75±40.96 min) but the dispatched number of helicopters did not increase during this period. The average arrival time of nearby passing ships (41.90±7.98 min) was the shortest. Conclusions: CMSRC efforts mitigated the growth of ship accidents despite increasing traffic volume. More dispatched rescue ships did not improve the SAR success rate without saving arrival time. Future SAR protocols may need to increase and strengthen the role of helicopters and nearby passing ships to improve the SAR success rate.

Global research trends in cardiac arrest research: a visual analysis of the literature based on CiteSpace.

BACKGROUND: The high morbidity, high mortality and low survival rate of cardiac arrest (CA) cause a heavy global burden. We aimed to analyze the changes in scientific output related to CA over the past two decades. METHODS: We analyzed the scientific output related to CA from 2000 to 2020 via the Web of Science. The data were analyzed using CiteSpace software. RESULTS: In total, 28,312 articles relating to CA were identified in the Web of Science. The volume of scientific research output in the field of global CA research was mainly distributed in the Americas, Europe and Asia, covering a wide range. Of the 28,312 articles, the research content of the highly cited literature mainly focused on CA, mild hypothermia treatment, and prognosis of CA patients. CONCLUSION: Various scientific methods were applied to reveal scientific productivity, collaboration, and research hotspots in the CA research field. Cardiopulmonary resuscitation (CPR), extracorporeal membrane oxygenation (ECMO), survival and target temperature management are research hotspots. Future research on CA will continue to focus on its treatment and prognosis to improve the survival rate of CA patients.

Immediate enteral nutrition can accelerate recovery and be safe in mild acute pancreatitis: A meta-analysis of randomized controlled trials.

OBJECTIVES: The effect of early enteral nutrition (EN) in patients with acute pancreatitis (AP) has been confirmed. In recent years, some researchers provided new strategy that immediate EN was offered after admission. The effect and safety of immediate EN was unclear because of the different results among studies. The study aimed to implement the meta analysis of randomized controlled trials (RCT) to confirm the effect and safety between the immediate EN group and the early refeeding group. METHODS: Four electronic databases including PubMed, EMBASE, the Cochrane Library and China National Knowledge Internet (CNKI) were searched from inception to July 2021. Endnote X7.0 software was used to manage all the relevant citations. Then data extraction and evaluation of risk of bias for included studies were performed after initial selection and full-text selection. All statistical analyses were performed by Review Manager 5.3 version software. RESULTS: 5 randomized controlled trials (RCT) involving 372 patients were included in the present study. The meta analysis revealed that immediate EN after admission in patients with AP could significantly decrease the length of hospital stay (LOHS) (Mean difference [MD] = 2.57, 95% confidence interval [CI] = 0.41-4.72) and the intolerance of feeding (risk ratio [RR] = 0.78, 95%CI = 0.63-0.95), compared with early refeeding. But immediate EN couldn't significantly decrease the incidence of readmission after discharging (RR = 0.51, 95%CI = 0.12-2.27), the incidence of progression to severe pancreatitis (RR = 0.76, 95%CI = 0.15-3.76), the incidence of complications (RR = 1.12, 95%CI = 0.50-2.49) and the values of C-reactive protein (CRP) and leukocyte counts (MD = 1.05, 95%CI = 0.15-2.26 and MD = 0.11, 95%CI = 0.59-0.80), compared with early refeeding. CONCLUSIONS: Compared with early refeeding, immediate EN after admission could safely reduce LOHS and intolerance of feeding in patients with AP.

Accuracy of eight intraocular lens power calculation formulas for segmented multifocal intraocular lens.

AIM: To evaluate the accuracy of eight different intraocular lens (IOL) power calculation formulas for a segmented multifocal IOL. METHODS: A total of 53 eyes of 41 adult cataract patients who underwent phacoemulsification and implantation with the SBL-3 segmented multifocal IOL between January 1, 2017 and January 31, 2019 were included in this retrospective study. Preoperative biometry measurements were obtained using an IOL Master. Manifest refraction was performed at least 4wk postoperatively. Accuracy of the eight formulas [Barrett Universal II, Emmetropia Verifying Optical (EVO), Haigis, Hill-RBF 2.0, Hoffer Q, Holladay 1, Kane, and SRK/T] was analyzed. RESULTS: Using current lens constants, all formulas exhibited errors of slight myopic shift in refractive prediction. The Barrett Universal II formula had a significantly lower median absolute error (MedAE) than did Holladay 1 (P=0.02), Kane (P=0.001) and Hill-RBF 2.0 (P<0.001) formulas. The Haigis formula had a lower MedAE value than did the Hill-RBF 2.0 formula (P=0.005). Differences in MedAE values among SRK/T, EVO and Hoffer Q formulas were not significant. After optimizing lens constants, the MedAE values of all formulas were reduced; significant changes were noted for EVO (P=0.022), Haigis (P=0.048), Hill-RBF 2.0 (P=0.014), Holladay 1 (P=0.045) and Kane (P=0.022) formulas. All formulas performed equally well after optimization of lens constants (P=0.203). CONCLUSION: All eight formulas tend to result in a myopic shift when using current lens constants. Optimized lens constants improve the accuracy of these formulas among adult Chinese patients.

Impact of co-blocking the costimulatory signals on immune-related genes after high-risk rabbit corneal allograft using 2nd-generation DNA sequencing technology.

The aim of this study was to evaluate the impact and mechanism of co-blocking of costimulatory signals CD28-B7-CD40-CD40L during immune allograft rejection. Forty-eight recipient rabbits were prepared as a high-risk corneal allograft model. After surgery, the animals were randomly divided into: control group, MR1 group, anti-B7 group, and co-blocking group (n=12, each group). Subconjunctival injection was first performed on the allograft surgery day until post-surgery day five. Four weeks later, or when immune rejection occurred, the cornea was sampled to detect and analyze the gene spectrum. The survival time in the co-blocking group was significantly longer than that in the other three groups (p < 0.05). Gene expression analysis revealed that the expression of genes associated with immune rejection, interleukin (IL)-1α, IL-1ß, intercellular cell adhesion molecule-1, and IL-2 was down-regulated in the co-blocking group, while IL-10 was up-regulated, but the changes in nuclear factor-κB and interferon-γ were not significant. In conclusion, the co-blocking of costimulatory signals can significantly reduce genes that promote corneal allograft rejection. The inhibition of corneal allograft rejection gene expression was significantly enhanced. These gene expression results can explain the conclusion of previous work at the genetic level.

Influence of severity and types of astigmatism on visual acuity in school-aged children in southern China.

AIM: To investigate the influence of astigmatism on visual acuity in school-aged children, and to define a cutoff for clinically significant astigmatism. METHODS: This is a population-based, cross-sectional study. Among 5053 enumerated children aged 5-15y in Guangzhou, 3729 (73.8%) children aged 7-15 with successful cycloplegic auto-refraction (1% cyclopentolate) and a reliable visual acuity measurement were included. Ocular measurement included external eye, anterior segment, media and fundus and cycloplegic auto-refraction. Primary outcome measures included the relationship between severity and subtypes of astigmatism and the prevalence of visual impairment. Three criteria for visual impairment were adopted: best-corrected visual acuity (BCVA) ≤0.7, uncorrected visual acuity (UCVA) ≤0.5 or <0.7 in the right eye. RESULTS: Increases of cylinder power was significantly associated with worse visual acuity (UCVA: ß=0.051, P<0.01; BCVA: ß=0.025, P<0.001). A substantial increase in UCVI and BCVI was seen with astigmatism of 1.00 diopter (D) or more. Astigmatism ≥1.00 D had a greater BCVI prevalence than cylinder power less than 1.00 D (OR=4.20, 95%CI: 3.08-5.74), and this was also true for hyperopic, emmetropic and myopic refraction categories. Oblique astigmatism was associated with a higher risk of BCVI relative to with the rule astigmatism in myopic refractive category (OR=12.87, 95%CI: 2.20-75.38). CONCLUSION: Both magnitude and subtypes of astigmatism influence the prevalence of visual impairment in school children. Cylinder ≥1.00 D may be useful as a cutoff for clinically significant astigmatism.

2,6-Bis(4H-1,2,4-triazol-4-yl)pyridine dihydrate.

The asymmetric unit of the title compound, C(9)H(7)N(7)·2H(2)O, comprises three formula units. The dihedral angles between the triazole rings and the respective central pyridine rings are 4.87 (16)/1.39 (17), 6.46 (16)/7.61 (16) and 7.00 (16)/3.77 (17)°. The water mol-ecules form O-H⋯O hydrogen bonds between themselves and O-H⋯N hydrogen bonds with the N-atom acceptors of the triazole rings, producing a three-dimensional framework.