Changes of brain functional network in Alzheimer's disease and frontotemporal dementia: a graph-theoretic analysis.

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two most common neurodegenerative dementias, presenting with similar clinical features that challenge accurate diagnosis. Despite extensive research, the underlying pathophysiological mechanisms remain unclear, and effective treatments are limited. This study aims to investigate the alterations in brain network connectivity associated with AD and FTD to enhance our understanding of their pathophysiology and establish a scientific foundation for their diagnosis and treatment. METHODS: We analyzed preprocessed electroencephalogram (EEG) data from the OpenNeuro public dataset, comprising 36 patients with AD, 23 patients with FTD, and 29 healthy controls (HC). Participants were in a resting state with eyes closed. We estimated the average functional connectivity using the Phase Lag Index (PLI) for lower frequencies (delta and theta) and the Amplitude Envelope Correlation with leakage correction (AEC-c) for higher frequencies (alpha, beta, and gamma). Graph theory was applied to calculate topological parameters, including mean node degree, clustering coefficient, characteristic path length, global and local efficiency. A permutation test was then utilized to assess changes in brain network connectivity in AD and FTD based on these parameters. RESULTS: Both AD and FTD patients showed increased mean PLI values in the theta frequency band, along with increases in average node degree, clustering coefficient, global efficiency, and local efficiency. Conversely, mean AEC-c values in the alpha frequency band were notably diminished, which was accompanied by decreases average node degree, clustering coefficient, global efficiency, and local efficiency. Furthermore, AD patients in the occipital region showed an increase in theta band node degree and decreased alpha band clustering coefficient and local efficiency, a pattern not observed in FTD. CONCLUSIONS: Our findings reveal distinct abnormalities in the functional network topology and connectivity in AD and FTD, which may contribute to a better understanding of the pathophysiological mechanisms of these diseases. Specifically, patients with AD demonstrated a more widespread change in functional connectivity, while those with FTD retained connectivity in the occipital lobe. These observations could provide valuable insights for developing electrophysiological markers to differentiate between the two diseases.

Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy.

PURPOSE: To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). METHODS: A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. RESULTS: The patients' median age was 37 years (range, 20-76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to -0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031). CONCLUSIONS: BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy.

Influence of Coal-Fired Fly Ash on Measurement Error of NO2 Electrochemical Sensors.

To overcome the limitations of NO2 electrochemical sensors, including their inaccurate measurements and short working life, when used around coal-fired power plants, we investigated the influence of coal-fired fly ash deposition on the measurement error of NO2 electrochemical sensors through experimental tests. The morphological characteristics and pellet diameter distribution of coal-fired fly ash pellets were determined via scanning electron microscopy. The sedimentation velocity of coal-fired fly ash pellets in the air was determined through theoretical calculations of aerodynamics and hydrodynamics. Additionally, the effect of the deposition of coal-fired fly ash on the measurement error of NO2 electrochemical sensors was determined through experimental tests. The test results show that the minimum and maximum measurement errors of the NO2 electrochemical gas sensor were 8.015% and 30.35%, respectively, after a deposition duration of 30 days with 30 mg/m3 coal-fired fly ash. This demonstrates that coal-fired fly ash deposition is the cause of the inaccurate measurements and short working life of these sensors. Coal-fired fly ash causes a decrease in the gas diffusion area of the sensor and the diffusion coefficient, thus increasing the sensor measurement error.

Increased neural activity of right temporo-parietal junction causes different effect on altruism in situations of advantageous and disadvantageous inequity.

Altruism is defined as the performance of "costly acts that confer economic benefits on other individuals", which is one of the major puzzles in the behavioural sciences today. Altruistic behaviour not only facilitates interpersonal adaptation and harmony but also enhances social welfare and social responsibility. The right temporo-parietal junction (rTPJ) has been proposed as playing a key role in guiding human altruistic behaviour, but its precise functional contribution to altruistic behaviour in situations of advantageous and disadvantageous inequity remains unclear. The purpose of this study was to modulate the activation of the rTPJ through transcranial direct current stimulation (tDCS) in order to clarify the causal role of the rTPJ in altruistic behaviour in situations of advantageous and disadvantageous inequity. A total of 106 participants were randomly assigned to one of three stimulation conditions: anodal tDCS stimulation on the rTPJ; sham tDCS stimulation on the rTPJ and anodal tDCS stimulation on the primary visual cortex (VC)as the control group, and. After 20 min of stimulation, participants undertook a modified dictator game that measured altruistic behaviour. Mixed-effect logistic regressions were applied to statistical analyses in this study. The results indicated that anodal tDCS over the rTPJ increased participants' altruistic tendency by increasing their tendency to choose altruistic options in trials with higher cost, as well as their tendency to behave altruistically in situations of advantageous but not disadvantageous inequity. These results suggested that increased neural activity of the rTPJ leads to different impacts on altruism in these two different inequity situations.

Molecular dynamics study on thermal conductance between a nanotip and a substrate under vertical forces and horizontal sliding.

The heat transfer between a nanotip and its substrate is extremely complex but is a key factor in determining the measurement accuracy in tip-assisted nanomanufacturing and thermometry. In this work, the heat transfer from the nanotip to the substrate during sliding is investigated using molecular dynamics simulations. Interfacial interaction and bond formation are analyzed during the sliding process. The results show that the increase of vertical force would greatly improve the interface thermal conductance between the nanotip and the substrate. It is found that more bonds are formed and there are larger contact areas at the interface. In addition, we found that the thermal conductivity of the nanotip is another obstacle for heat transfer between the tip and substrate and it is greatly limited by the nanotip diameter near contact which is close to or even smaller than the phonon mean free path. Meanwhile, the dynamic formation and breakage of the covalent bonds during the sliding could gradually smoothen the tip apex and enhance the thermal transport at the interface. This work provides guidance for the thermal design of a nanotip-substrate system for nanoscale thermal transport measurements.

Genetic analysis and clinical features of three Chinese patients with Oguchi disease.

BACKGROUND: Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness caused by disease-causing variants in the rhodopsin kinase gene (GRK1) or the arrestin gene (SAG). Our study aims to describe the clinical features and identify the genetic defects for three Chinese patients with Oguchi disease. METHODS: We conducted detailed ophthalmologic examinations for three patients from three unrelated non-consanguineous Chinese families. Targeted next-generation sequencing (targeted NGS) and copy number variations (CNVs) analysis were applied to screen pathogenic variants. Sanger sequencing validation, quantitative real-time PCR (qPCR), and segregation analysis were further performed for confirmation. Subsequently, a combined genetic and structural biology approach was used to infer the likely functional consequences of novel variants. RESULTS: All three patients presented with typical clinical features of Oguchi disease, including night blindness, characteristic fundus appearance (Mizuo-Nakamura phenomenon), attenuated rod responses, and negative ERG waveforms. Their visual acuity and visual field were normal. Genetic analysis revealed two pathogenic variants in SAG and four pathogenic variants in GRK1. Patient 1 was identified to harbor compound heterozygous SAG variants c.874C > T (p.R292*) and exon2 deletion. Compound heterozygous GRK1 variants c.55C > T (p.R19*) and c.1412delC (p.P471Lfs*52) were found in patient 2. In patient 3, compound heterozygous GRK1 variants c.946C > A (p.R316S) and c.1388 T > C (p. L463P) were detected. CONCLUSIONS: We reported the first two Chinese Oguchi patients with novel GRK1 pathogenic variants (P471Lfs*52, R316S, L463P) and one Oguchi case with SAG, indicating both GRK1 and SAG are important causative genes in Chinese Oguchi patients.

Anomaly Detection of Wind Turbine Driveline Based on Sequence Decomposition Interactive Network.

Aimed at identifying the health state of wind turbines (WTs) accurately by using the comprehensive spatio and temporal information from the supervisory control and data acquisition (SCADA) data, a novel anomaly-detection method called decomposed sequence interactive network (DSI-Net) is proposed in this paper. Firstly, a DSI-Net model is trained using preprocessed data from a healthy state. Subsequences of trend and seasonality are obtained by DSI-Net, which can dig out underlying features both in spatio and temporal dimensions through the interactive learning process. Subsequently, the trained model processes the online data and calculates the residual between true values and predicted values. To identify anomalies of the WTs, the residual and root mean square error (RMSE) are calculated and processed by exponential weighted moving average (EWMA). The proposed method is validated to be more effective than the existing models according to the control experiments.

Leber congenital amaurosis as an initial manifestation in a Chinese patient with thiamine-responsive megaloblastic anemia syndrome.

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder, inherited by the defective SLC19A2 gene that encodes a high-affinity thiamine transporter (THTR-1). TRMA is characterized by the occurrence of classical triad manifestations including megaloblastic anemia, diabetes mellitus, and sensorineural deafness. In addition to the systemic manifestations, ophthalmic features can be present and include retinitis pigmentosa, optic atrophy, cone-rod dystrophy, maculopathy, and Leber congenital amaurosis. Here we report a 6-year-old boy presenting severe early-onset retinal dystrophy with the initial diagnosis of Leber congenital amaurosis, which followed for 12 years. Diabetes mellitus occurred 3 years after vision problem. Eosinophilic granuloma of the left scapula was confirmed at 13 years old. Whole-exome sequencing was performed to identify two novel compound heterozygous variants c.725dupC (p.Ala243Serfs*3) and c.121G>A (p.Gly41Ser) in SLC19A2 gene (NM_006996.3). Oral thiamine supplementation treatment was initiated at 13 years. This case demonstrates Leber congenital amaurosis can present as the first clinical feature before systemic manifestations. Phenotypic variety should be aware and multidisciplinary teamwork and regular follow-up are important for TRMA patient care.

Distinct roles of the medial prefrontal cortex in advantageous and disadvantageous inequity aversion.

Human beings have a strong preference for the fair distribution of resources in situations of both advantageous and disadvantageous inequity. Neuroimaging studies have shown that the process of advantageous and disadvantageous inequity aversion involves distinct brain regions. However, little is known about the causal roles of the dorsal medial prefrontal cortex (dmPFC) in these two types of inequity aversion. To clarify the roles of the dmPFC in both types of inequity aversion, 70 subjects were recruited and randomly assigned to two anodal transcranial direct current stimulation (tDCS) groups: tDCS over the dmPFC and tDCS over the primary visual cortex. Participants then completed a dictator game, which was used to measure the aversion to inequity. This study found that tDCS over the dmPFC decreased the aversion to disadvantageous inequity, but not that to advantageous inequity, and the treatment effect was modulated by equity cost. These results show that the dmPFC plays different roles in these two types of inequity aversion.

A novel tandem duplication of PRDM13 in a Chinese family with North Carolina macular dystrophy.

PURPOSES: North Carolina macular dystrophy (NCMD) is a rare autosomal dominant inherited disorder characterized by macular impairment with a variety of phenotypic manifestations. The aims of this study were to assess the clinical features of a Chinese family with NCMD and to identify the underlying genetic cause of the disease. METHODS: Three patients from a Chinese family were included in this study. Detailed ophthalmological examinations were performed, including best corrected visual acuity (BCVA), slit lamp, dilated indirect ophthalmoscopy, fundus photography, optical coherence tomography (OCT), fundus autofluorescence, full-field electroretinography (ERG), and electrooculography (EOG). Genomic DNA was extracted from peripheral blood samples. Whole-genome sequencing and long-read genome sequencing were applied to detect the pathogenic variants. Sanger sequencing was performed to confirm the breakpoints. RESULTS: All three patients had macular involvement ranging from patchy yellowish-white lesions to big-area thinning, which are typical for NCMD. The BCVA ranged from 20/50 to 20/20. OCT revealed varying degrees of macular structure disorganization. The ERG responses were normal, and the Arden ration of the EOG was reduced. A novel 134.6 kb (g.99932464-100067110dup) tandem duplication on chromosome 6 (NC_000006.11) encompassing the entire CCNC and PRDM13 genes and a DNase 1 hypersensitivity site in the MCDR1 locus was identified. CONCLUSION: A novel large tandem duplication in MCDR1 locus was confirmed in a Chinese family with NCMD with a variety of macular phenotypes.

Disrupted intraflagellar transport due to IFT74 variants causes Joubert syndrome.

PURPOSE: Ciliopathies are a group of disorders caused by defects of the cilia. Joubert syndrome (JBTS) is a recessive and pleiotropic ciliopathy that causes cerebellar vermis hypoplasia and psychomotor delay. Although the intraflagellar transport (IFT) complex serves as a key module to maintain the ciliary structure and regulate ciliary signaling, the function of IFT in JBTS remains largely unknown. We aimed to explore the impact of IFT dysfunction in JBTS. METHODS: Exome sequencing was performed to screen for pathogenic variants in IFT genes in a JBTS cohort. Animal model and patient-derived fibroblasts were used to evaluate the pathogenic effects of the variants. RESULTS: We identified IFT74 as a JBTS-associated gene in three unrelated families. All the affected individuals carried truncated variants and shared one missense variant (p.Q179E) found only in East Asians. The expression of the human p.Q179E-IFT74 variant displayed compromised rescue effects in zebrafish ift74 morphants. Attenuated ciliogenesis; altered distribution of IFT proteins and ciliary membrane proteins, including ARL13B, INPP5E, and GPR161; and disrupted hedgehog signaling were observed in patient fibroblasts with IFT74 variants. CONCLUSION: IFT74 is identified as a JBTS-related gene. Cellular and biochemical mechanisms are also provided.

Clinical characterization and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7.

Purpose: To evaluate the retinal phenotype and genetic features of Chinese patients with spinocerebellar ataxia type 7 (SCA7). Methods: Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography, were performed to analyse the retinal lesions of patients with SCA7. A molecular genetic analysis was completed to confirm the number of CAG repeats in ATXN7 gene on the patients and their family members. Results: Eight patients from three families with SCA7 were included in this study. Trinucleotide repeat was expanded from 43 to 113 in the affected patients. The affected patients were characterized by different degrees of cone-rod dystrophy, which is positively related to the number of CAG repeats and age. All patients complained of progressive bilateral visual loss, and most cases reported visual disturbance earlier than gait movement or dysarthria. A coarse granular appearance of the macular region on scanning laser ophthalmoscopy, hypofluorescence in the macula on autofluorescence, retinal atrophy on optic coherence tomography, depression of multifocal electroretinograms and prominent abnormalities in cone-mediated responses on electrograms are the general features of SCA7-related retinopathy. Hyperreflective dots in the outer retinal layers and choroidal vessel layers are a common sign in optic coherence tomography in the advanced stage. Conclusions: SCA7 shows a cone-rod dystrophy phenotype. The multimodal imaging of the retina is beneficial to detect the early lesions of cone-rod dystrophy related to SCA7.

Clinical and genetic analysis of the ABCA4 gene associated retinal dystrophy in a large Chinese cohort.

ABCA4 gene associated retinal dystrophies (ABCA4-RD) are a group of inherited eye diseases caused by ABCA4 gene mutations, including Stargardt disease, cone-rod dystrophy and retinitis pigmentosa. With the development of next-generation sequencing (NGS), numerous clinical and genetic studies on ABCA4-RD have been performed, and the genotype and phenotype spectra have been elucidated. However, most of the studies focused on the Caucasian population and limited studies of large Chinese ABCA4-RD cohorts were reported. In this study, we summarized the phenotypic and genotypic characteristics of 129 Chinese patients with ABCA4-RD. We found a mutation spectrum of Chinese patients which is considerably different from that of the Caucasian population and identified 35 novel ABCA4 mutations. We also reported some rare and special cases, such as, pedigrees with patients in two generations, patients diagnosed with cone-rod dystrophy or retinitis pigmentosa, patients with subretinal fibrosis and patients with preserved foveal structure. At the same time, we focused on the correlation between the genotypes and phenotypes. By the comprehensive analysis of multiple clinical examinations and the application of multiple regression analysis, we proved that patients with two "null" variants had a younger onset age and reached legal blindness earlier than patients with two "none-null" variants. Patients with one or more "none-null" variants tended to have better visual acuity and presented with milder fundus autofluorescence changes and more preserved rod functions on the full-field electroretinography than patients with two "null" variants. Furthermore, most patients with the p.(Phe2188Ser) variant shared a mild phenotype with a low fundus autofluorescence signal limited to the fovea and with normal full-field electroretinography responses. Our findings expand the variant spectrum of the ABCA4 gene and enhance the knowledge of Chinese patients with ABCA4-RD.

Novel variants in PNPLA6 causing syndromic retinal dystrophy.

PNPLA6-related disorders include several phenotypes, such as Boucher-Neuhäuser syndrome, Gordon Holmes syndrome, spastic paraplegia, photoreceptor degeneration, Oliver-McFarlane syndrome and Laurence-Moon syndrome. In this study, detailed clinical evaluations and genetic testing were performed in five (4 Chinese and 1 Caucasian/Chinese) syndromic retinal dystrophy patients. Genotype-phenotype correlations were analyzed based on review of the literatures of previously published PNPLA6-related cases. The mean age of patients and at first visit were 20.8 years (11, 12, 25, 28, 28) and 14.2 years (4, 7, 11, 24, 25), respectively. They all presented with severe chorioretinal dystrophy and profoundly decreased vision. The best corrected visual acuity (BCVA) ranged from 20/200 to 20/2000. Systemic manifestations included cerebellar ataxia, hypogonadotropic hypogonadism and hair anomalies. Six novel and three reported pathogenic variants in PNPLA6 (NM_001166111) were identified. The genotypes of the five cases are: c.3134C > T (p.Ser1045Leu) and c.3846+1G > A, c.3547C > T (p.Arg1183Trp) and c.1841+3A > G, c.3436G > A (p.Ala1146Thr) and c.2212-10A > G, c.3436G > A (p.Ala1146Thr) and c.2266C > T (p.Gln756*), c.1238_1239insC (p.Leu414Serfs*28) and c.3130A > G (p.Thr1044Ala). RT-PCR confirmed that the splicing variants indeed led to abnormal splicing. Missense variants p.Thr1044Ala, p.Ser1045Leu, p.Ala1146Thr, p.Arg1183Trp and c.3846+1G > A are located in Patatin-like phospholipase (Pat) domain. In conclusion, we report the phenotypes in five patients with PNPLA6 associated syndromic retinal dystrophy with variable systemic involvement and typical choroideremia-like fundus changes. Ocular manifestations may be the first and the only findings for years. All of our patients carried one severe deleterious variant (stop-gain or splicing variant) and one milder variant (missense variant). Retinal involvement was significantly correlated with severe deleterious variants and variants in Pat domain.

The only-child effect in the neural and behavioral signatures of trust revealed by fNIRS hyperscanning.

In daily life, trust is important in interpersonal interactions. However, little is known about interpersonal brain synchronization with respect to trust; in particular, the differences between individuals with and without siblings are not clear. Therefore, this study applied functional near-infrared spectroscopy hyperscanning in a sequential reciprocal-trust task. We divided pairs of participants (strangers) into two groups according to their only-child status. The two strangers interacted with one another in an online trust game while their brain activities in the medial prefrontal cortex (mPFC) and the right temporoparietal junction (rTPJ) were measured. The behavioral results revealed that compared with the non-only-child group, the only-child group exhibited lower repayment, less reciprocation, and less cooperative decisions during the process. In addition, the brain imaging results showed that the interpersonal synchronization of the mPFC in the only-child group was significantly weaker than that in the non-only-child group. Our findings demonstrate neurobehavioral support for the only-child effect in terms of the trust by revealing that an only child shows less trust than does a non-only-child, resulting in lower inter-brain coherence.

Treating Bietti crystalline dystrophy in a high-fat diet-exacerbated murine model using gene therapy.

Lipid metabolic deficiencies are associated with many genetic disorders. Bietti crystalline dystrophy (BCD), a blindness-causing inherited disorder with changed lipid profiles, is more common in Chinese and Japanese than other populations. Our results reveal that mouse models lacking Cyp4v3 have less physiological and functional changes than those of BCD patients with this gene defect. After the administration of a high-fat diet (HFD), the occurrence of retinal lesions were both accelerated and aggregated in the Cyp4v3-/- mouse models, implying that changed lipid levels were not only associated factors but also risk factors to BCD patients. Facilitated by the results, we found that the reduced electroretinography waveforms and retinal thickness observed in the HFD-induced mouse models were effectively recovered after subretinal delivery of a human CYP4V2 gene carried by an adeno-associated virus vector, which demonstrates the potential curability of BCD by gene therapy.

Detailed comparison of phenotype between male patients carrying variants in exons 1-14 and ORF15 of RPGR.

PURPOSE: To compare disease severity in detail between patients carrying variants in exons 1-14 and ORF15 of retinitis pigmentosa GTPase regulator (RPGR). METHODS: Systematic next-generation sequencing data analysis, Sanger sequencing validation and segregation analysis were utilised to identify the pathogenic variants. Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography were performed. Statistical analysis, including age adjustment and comparison, were performed based on cross-sectional level to compare disease severity between variants in the two RPGR variant groups. RESULTS: Sixty-two variants were identified in RPGR in 86 patients from 77 unrelated families. Twenty-nine (37.7%) had variants in RPGR-exons 1-14 (group 1) and 48 (62.3%) in RPGR-ORF15 (group 2). Eighty-four patients were diagnosed with X-linked retinitis pigmentosa and only two patients with cone-rod dystrophy. LogMAR visual acuity increased 0.035 and 0.022 each year on average in group 1 and group 2, respectively. Group 2 patients had better visual acuity with a mean logMAR difference of 0.4378, which is significant after age adjustment (P < 0.01). Neither the value of log (ellipsoid zone width) nor central retinal thickness was significantly correlated with variant grouping after considering the effect of the age variable (P = 0.56 and 0.40, respectively). Spherical refractive error did not differ significantly between the two variant groups (P = 0.17). Patterns of autofluorescence included a hyperfluorescent ring at the posterior pole, diffuse hyperfluorescence in the macular area, and dark macular autofluorescence with or without fovea hyperfluorescence. The age and proportion of fundus autofluorescence patterns between the two variant groups were significantly different (P < 0.01). CONCLUSIONS: Patients with variants in exons 1-14 retained less visual acuity than patients with ORF15 variants and deteriorated faster. However, the ellipsoid zone widths, central retinal thickness and refractions were comparable between the two groups. Autofluorescence pattern relates to the age and the variant grouping.

TNFRSF21 mutations cause high myopia.

BACKGROUND: High myopia (HM) is one of the leading causes of vision impairment worldwide, accompanied by a series of pathological ocular complications. Studies have shown that genetic factors play an important role in the pathogenesis of HM. The aim of our study is to identify a candidate gene for a large family with non-syndromic HM. METHODS: A large Chinese family, including 12 patients with non-syndromic HM, and 220 unrelated patients with HM, were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital. Three affected subjects from the large family were selected to perform whole exome sequencing (WES). Rare heterozygous variants shared by all three subjects were retained and then Sanger sequencing was used to determine whether any of the remaining variants cosegregated with the disease phenotype. Furthermore, all coding regions of the candidate genes were analysed in 220 unrelated patients with HM. Immunofluorescence assay was used to detect the expression of the candidate gene in the eye. Annexin V/PI staining and flow cytometry were applied to detect cell apoptotic changes. RESULTS: WES identified a novel TNF receptor superfamily member 21 (TNFRSF21) variant, P146A, in a large Chinese family with HM, and another three rare heterozygous variants (P202L, E240* and A440G) in TNFRSF21 were found in 220 unrelated cases with HM. Immunofluorescence assay indicated that it is strongly expressed in the mouse eye. Compared with the wild type, the P146A variant could significantly increase adult retinal pigment epithelial cell line-19 cell apoptotic levels. CONCLUSIONS: Variants in TNFRSF21 cause non-syndromic HM in Chinese population.

CLINICAL CHARACTERISTICS AND MOLECULAR GENETIC ANALYSIS OF A COHORT OF CHINESE PATIENTS WITH CHOROIDEREMIA.

PURPOSE: To describe the clinical and molecular genetic characteristics of a large cohort of Chinese patients with choroideremia (CHM). METHODS: Forty-eight Chinese participants from 35 families with a clinical diagnosis of CHM who harbored sequence variants in the CHM gene were enrolled. Comprehensive clinical evaluations and molecular genetic analysis of the CHM gene were performed. RESULTS: The median age of the 48 patients was 31.5 years (range, 5-78 years). There were 30 different sequence variants detected in 35 families; of which, 13 sequence variants were novel. The mean (±SD) best-corrected visual acuity best in logarithm of the minimum angle of resolution equivalents was 0.71 (±0.87) (range, 0.00-2.80) or approximately 20/100 in Snellen visual acuity. A significant correlation was revealed between best-corrected visual acuity best and age (P < 0.001). The trend in the change in the best-corrected visual acuity over age showed that relatively good vision remained until 20 years old. The patterns of fundus photography and fundus autofluorescence finding demonstrated that residual retinal pigment epithelium areas significantly declined in patients at the age of 20 years or older. The results of visual field and full-field electroretinography showed that these measures might be of limited value for evaluating the condition of the late stage of CHM in Chinese patients. CONCLUSION: This study described for the first time the clinical and molecular genetic characteristics of a large cohort of Chinese patients with CHM. The findings from best-corrected visual acuity best and visual field showed that the impairment of visual function in CHM might be more severe in Chinese patients than in western patients.

[Design and Implementation of Infusion Monitor Software Based on C# Language].

OBJECTIVE: To design an infusion monitor software and implement the establishment of wireless intelligent infusion monitoring system in hospital infusion area combined with the existing platform equipment in the laboratory. METHODS: On the platform of Visual Studio 2013, C# language was used to realize the software development of the upper computer, and the data from infusion monitoring equipment was received through WiFi wireless transmission technology. RESULTS: The upper computer software had a friendly user interface, and it could receive infusion data correctly and display normally. The upper computer software had alarm function and good performance. CONCLUSIONS: Infusion monitor software can realize comprehensive monitoring of multiple infusion monitors and real-time monitor of infusion process. It is easy to operate and carry which is helpful to improve the efficiency and quality of medical care.