Catastrophic health expenditure (CHE) is a key indicator for studying the economic burden of diseases. Previous study mainly focused on exploring the relationship between severe diseases such as cancer and multimorbidity with CHE. However, there is a lack of research exploring the differential effects of single and multiple chronic diseases on CHE. This study aims to analyse the longitudinal association between different chronic disease conditions and CHE among elderly households in China, and investigate whether this association is influenced by other demographic and socioeconomic variables. A total of 6,483 older adults obtained from four waves (2013, 2015, 2018, 2020) of the China Health and Retirement Longitudinal Study (CHARLS) were analysed (elderly household without CHE at baseline were included). CHE was defined as out-of-pocket health expenditures exceeding 40

Background Dyslipidemia is a major risk factor for cardiovascular diseases, but its prevalence and determinants among sedentary occupational population are poorly understood. This study aimed to investigate the prevalence and associated factors for dyslipidemia among a sedentary occupational population in Shanghai, China. Methods We collected data from 35,950 sedentary occupational workers on their demographics, social, medical, and family history, lifestyle, anthropometry, and biochemistry. We used the 2016 Chinese guideline for the management of dyslipidemia in adults to define dyslipidemia and its subtypes. We performed multivariate logistic regression to examine the factors associated with dyslipidemia. Results The prevalence of dyslipidemia was 29.10%, with 15.86% for high triglycerides (TG), 6.43% for high total cholesterol (TC), 5.37% for high low-density lipoprotein cholesterol (LDL-C), and 14.68% for low high-density lipoprotein cholesterol (HDL-C). Men had a significantly higher prevalence of dyslipidemia than women (39.64% vs. 12.43%, P < 0.01). Factors associated with dyslipidemia included older age, being married, longer sedentary time while resting, frequent intake of animal viscera, current smoking, hypertension, diabetes, and obesity. Current drinking was associated with a 1.24 times higher prevalence of high TG ( P < 0.01). Current smokers were less likely to have low HDL-C than non-smokers. Conclusions Our present study, in a population of 35,950 sedentary occupational workers from Shanghai, demonstrated a prevalence of dyslipidemia, but lower than in other previous studies without the limitation of occupational characteristics. Prevention and control measures for dyslipidemia should take into account the characteristics and related factors for this population group.

Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.

Purpose: The purpose of this study was to investigate the clinical and genetic characteristics of the retinitis pigmentosa GTPase regulatory factor gene (RPGR) in a Chinese cohort. Methods: A retrospective analysis was performed on 80 subjects with RPGR-retinal dystrophy (RPGR-RD) for detailed genetic and clinical characterization. The panel-based next-generation sequencing of 792 causative genes involved in common genetic eye diseases was conducted in all individuals, followed by clinical variant interpretation. Information, including age, sex, geographic distribution, family history, consanguineous marriage, age at symptom onset, disease duration, best corrected visual acuity (BCVA), and complete ophthalmologic examination results, was collected. Results: This cohort (41 men and 39 women) included 26 families (26 probands and their available family members) and 13 sporadic cases. The average age of these participants was 36.35 ± 17.68 years, and the majority of the families were from eastern China (28 families, 71.79%). The average duration of disease in the probands was 22.68 ± 15.80 years. In addition, the average BCVA values of the right and left eyes in the probands were 0.96 ± 0.77 and 1.00 ± 0.77, respectively. A total of 34 RPGR variants were identified, including 6 reported variants and 28 novel variants. Among these variants, NM_001034853.1: c.2899_2902delGAAG and c.2744_2745ins24 were considered de novo variants. The majority of the RPGR variants were classified as likely pathogenic, accounting for 70.59% of the variants (24 variants). The most common nucleotide and amino acid changes identified in this study were deletions (16 variants, 45.06%) and frameshifts (17 variants, 50.00%), respectively. Genetic analysis revealed that these RPGR variants were distributed in 10 different subregions of RPGR, and 70.59% of the RPGR variants (24 variants) were located in exon 15. Four RPGR variants, NM_001034853.1: c.2405_2406delAG, c.1345C > T, c.2218G > T and c.2236_2237delGA, occurred at a very high frequency of 28.21% (11 families) among 39 unrelated families. Conclusion: This study expands the known mutational spectrum of RPGR, and we provide a new reference for the genetic diagnosis of RPGR variants.

Glaucoma, a common cause of blindness, is characterized by the progressive loss of retinal ganglion cells (RGCs). Growing evidence suggests that nobiletin (NOB) is a promising neuroprotective drug; however, its effects on glaucomatous neurodegeneration remain unknown. Using rat models of microbead occlusion in vivo and primary RGCs model of hypoxia in vitro, we first demonstrate that NOB reduces RGC apoptosis by a TUNEL assay, Hoechst 33342 staining and FluoroGold (FG) retrograde labeling. This effect does not depend on intraocular pressure (IOP) lowering. Additionally, NOB partially restored the functional and structural damage of inner retinas, attenuated Müller glial activation and oxidative stress caused by ocular hypertension. At 2 weeks after IOP elevation, NOB further enhanced Nrf2/HO-1 pathway in RGCs to withstand the cumulative damage of ocular hypertension. With the administration of HO-1 inhibitor tin-protoporphyrin IX (SnPP), the protective effect of NOB was attenuated. Overall, these results indicate that NOB exerts an outstanding neuroprotective effect on RGCs of glaucomatous neurodegeneration. Besides, interventions to enhance activation of Nrf2/HO-1 pathway can slow the loss of RGCs and are viable therapies for glaucoma.

Purpose Retinitis pigmentosa (RP) constitutes a class of common inherited retinal dystrophies. Patients with RP and comorbid primary angle-closure glaucoma (PACG) have been described, but the relationship between the diseases remains unclear. This study investigated the clinical and genetic characteristics of Chinese patients with RP and comorbid PACG. Methods Of 1356 patients with RP, we analyzed the genetic features of 39 RP patients with PACG using next-generation sequencing and reviewed their clinical characteristics. Results In total, 18 patients with acute PACG and 21 patients with chronic PACG were included in this study; their age at examination was 50.54 +/- 12.99 years (range, 25.0-71.0 years), and their age at PACG onset was 46.04 +/- 14.50 years (range, 24.9-68.0 years). Additionally, the mean lens thickness (LT) was 4.49 +/- 0.44 mu m, and the mean axial length (AL) was 22.63 +/- 1.17 mm. Notably, the prevalence of PACG in patients with RP was 2.88%; this was higher than the prevalence in the general population. This could be explained by nanophthalmos, thickened lentis, ectopia lentis, or zonular insufficiency. Furthermore, patients with a shorter AL, a greater LT, iridociliary cysts, or nanophthalmos exhibited earlier development of PACG. Overall, 30 disease-causing variants spanning 17 genes were identified in 56.41% of the patients, and PRPH2 was the most common mutation gene. Conclusions Our findings revealed that there is a strong association between RP and PACG. Furthermore, intraocular pressure (IOP) should be measured in patients with RP to protect them from the aggravated damage of an elevated IOP.

Recent research has shown that genetic variations in the oxytocin receptor (OXTR) may be related to variations in subtypes of obsessive compulsive disorder (OCD). We aimed to explore the relationship between different subtypes of OCD and the genetic variation between rs1316193 and rs4686301 of the OXTR. In this case-control study, 92 OCD patients and 92 healthy controls were included in the OCD and control groups, respectively. The Y-BOCS scale was used to assess the severity of the OCD symptoms. The fasting peripheral blood samples were collected to extract DNA. rs4686301 and rs13316193 were genotyped using restriction fragment length polymorphism analysis techniques. Whether the gene frequency of the locus and the distribution of allele frequency were related to OCD were further study by TaqMan allele typing. The rs4686301 locus differed significantly between behavior and control groups. The genotype frequency and allele frequency at the rs4686301 locus were statistically significant between behavior and control groups (P<0.05). There was significant difference in the genotype frequency at the rs13316193 locus between behavior and control groups (P<0.05). The rs4686301 polymorphism of the OXTR may affect the clinical subtype of OCD. The rs13316193 polymorphism of the OXTR may be a risk factor for obsessive-compulsive behavior.

Background To date, certain efforts have been made to investigate the clinical and genetic characteristics of patients with EYS mutations. However, data for Chinese patients are limited. Objectives To perform a detailed phenotyping and genetic characterization of 55 Chinese patients with EYS -RD, and to identify risk factors for these clinical data. Methods A total of 55 patients with EYS -RD were recruited. Best-corrected visual acuity (BCVA), patient age, age at symptom onset, disease duration, and genetic information were collected. Results Thirty-six novel variants, three hot mutations of EYS (30.3%, c.6416G>A, c.6557G>A, c.7492G>C) and one hot region (49.06%, Laminin G domains) were identified. In all, 36.84% of the mutations occurred at base G site, and majority of mutations (56.56%) were missense. Late-truncating mutations are significantly more prevalent (41.30%). The mean age of onset was 15.65 ± 14.67 years old; it had no significant correlation with genotype. The average BCVA was 0.73 ± 0.93 LogMAR, and 61.8% of eyes had a BCVA better than 0.52 logMAR. BCVA was positively correlated with disease duration time. The mean MD was 23.18 ± 7.34 dB, MD showed a significant correlation with genotype and age. Cataract was present in 56.45% of patients, and 42.59% of patients showed an absence of pigmentation in the retina. Cataract and hyperpigmentation both showed a significant correlation with age. Conclusions EYS-RD is associated with a moderate phenotype with onset around adolescence, but great variability. Our study largely enhances the current knowledge of phenotypic and genotypic characteristics of EYS -RD, which could pave the way for better management of these patients.

Purpose: Stargardt disease (STGD) is the most frequent cause of hereditary macular dystrophy in childhood. Variants in the ABCA4, ELOVL4, PROM1, BEST1, and PRPH2 genes have been detected in patients with autosomal recessive or dominant STGD. This study was aimed at identifying the novel disease-associated variants in Chinese patients with STGD. Methods: Ten Chinese families and two sporadic cases with STGD (n = 32) were enrolled in the study. All subjects underwent genetic analysis with next-generation sequencing (NGS), which was based on a specially customized capture panel targeting exons and untranslated regions (UTRs) of 792 genes related to common hereditary ophthalmopathy. Variants were analyzed to assess possible pathogenicity. Results: Fourteen disease-associated variants of ABCA4 were detected in 9 Chinese families with autosomal recessive STGD, including 11 pathogenic variants and 3 likely pathogenic variants. Variant c.4253 + 4C > T in ABCA4 was identified as one de novo variant. Of the 14 distinct variants in ABCA4, 7 novel variants were found. In addition, one known variant of PROM1, c.1117C > T (p.Arg373Cys), was detected in one family and one sporadic case with autosomal dominant STGD, respectively. One novel missense variant of ELOVL4, c.59A > G (p.Asn20Ser), was found in one sporadic case with autosomal dominant STGD. The potential deleterious effects of these novel variants were confirmed through intensive analysis. Conclusion: By panel-based NGS, 8 novel disease-associated variants are identified in two genes responsible for STGD, including ABCA4 and ELOVL4. Our results further extend the mutation spectrum of these two genes in Chinese patients with STGD. One ABCA4 c.4253 + 4C > T variant is identified as a de novo splicing variant.

Additional file 3 : Table S3. The patients suspected with STL1.

Background To report the clinical and genetic findings from seven Chinese patients with choroideremia. Methods Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (NGS) was performed on samples from all patients. Detailed clinical characteristics of the patients with choroideremia identified in this study were assessed using multimodal imaging. Results Seven patients with choroideremia were identified, and six novel variants in CHM (c.1960 T > C p.Ter654Gln, c.1257del p.Ile420*fs1, c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35, c.1414-2A > T, and c.1213C > T p.Gln405Ter, c.117-1G > A) were revealed. All variants were deleterious mutations: two were frameshifts, two were nonsense mutations, two were splicing mutations, and one was a readthrough mutation. The clinical phenotypes of these patients were markedly heterogeneous, and they shared many common clinical features with RP, including night blindness, constriction of the visual field and gradually reduced visual acuity. However, patients with choroideremia showed pigment hypertrophy and clumping, and chorioretinal atrophy, and a majority of patients with choroideremia presented with retinal tubulations in the outer layer of the retina. Conclusions We provide a detailed description of the genotypes and phenotypes of seven patients with choroideremia who were accurately diagnosed using NGS. These findings provide a better understanding of the genetics and phenotypes of choroideremia.

PURPOSE. To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. METHODS. Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. RESULTS. The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. CONCLUSIONS. To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.

PURPOSE:To provides the clinical and genetic characteristics of a series of Chinese patients with X-linked juvenile retinoschisis (XLRS) through multimodal imaging and next-generation sequencing.METHODS:Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed.RESULTS:Twenty-five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best-corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X-linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype-phenotype association was observed.CONCLUSION:This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype-phenotype correlations were found.

Background Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present. Methods By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1. Results There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found. Conclusions Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.

Background Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present. Methods By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1. Results There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found. Conclusions Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.

Citation for published version (APA): Gao, F-J., Wang, D-D., Chen, F., Sun, H-X., Hu, F-Y., Xu, P., Li, J., Liu, W., Qi, Y-H., Li, W., Wang, M., Zhang, S., Xu, G-Z., Chang, Q., & Wu, J-H. (2021). Prevalence and genetic-phenotypic characteristics of patients with USH2A mutations in a large cohort of Chinese patients with inherited retinal disease. British Journal of Ophthalmology, 105(1), 87-92. https://doi.org/10.1136/bjophthalmol-2020-315878

Additional file 2: Table S2. Twenty-one ABCA4 variants identified in this study and their in silico functional assessment.

AimsTo investigate the frequency of USH2A mutation and the clinical and genetic differences between Usher syndrome type II (USH2) and retinitis pigmentosa (RP) in a large cohort of Chinese patients.MethodsA total of 1381 patients with inherited retinal disease (IRD) were recruited. The phenotypic and genotypic information of patients with USH2A mutations was evaluated.ResultsThe prevalence of patients with USH2A mutations was 15.75%, which was the most frequently detected gene in this cohort of patients. Hotspot of USH2A mutations was c.8559-2A >G and c.2802T >G. Patients with USH2 had an earlier and more serious decline of visual function and damage to retina structure than did patients with RP in the first 10 years (p<0.05), but there was no difference in the visual prognosis between the two groups when the course of disease exceeded 10 years (p>0.05). Missense variants had less severe consequences and were found more commonly in RP, whereas more deleterious genotypes were associated with an earlier onset of disease and were found more commonly in USH2.ConclusionsThis study provides detailed clinical–genetic assessment of patients with USH2A mutations of Chinese origin, enabling precise genetic diagnoses, better management of these patients and putative therapeutic approaches.

Purpose: To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population. Design: Cohort study. Participants: A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 2701) were recruited. Methods: All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation. Main Outcome Measures: Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing. Results: Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup (<= 5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6-16 years old, 73.74%) and late-onset subgroup (>= 17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP. Conclusions: This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum iscompletely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to familymembers. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in China. (C) 2019 by the American Academy of Ophthalmology

Purpose: To explore a method for the early, rapid and accurate diagnosis of Wolfram syndrome 1 (WS1) and further enrich the spectrum of WFS1 mutations in the Chinese population. Methods: We analyzed 279 patients with unexplained optic atrophy using next-generation sequencing. All patients underwent detailed clinical evaluations. Furthermore, Sanger sequencing and cosegregation analyses were performed within families. Results: Five patients with WS1 were identified in four unrelated families, and their clinical features were reviewed in detail. Seven variants of WFS1 were detected, including three reported variants (p.G674R, p.Tyr508Cysfs*34, and p.G702D) and four novel variants (p.W540G, p.K634*, p.F770C, and p.Q584P). Furthermore, the variant p.G674R was recurrent. Conclusion: Considering that WS1 is a rare progressive neurodegenerative disease, early diagnosis is beneficial to the systematic evaluation, monitoring and management of complications to improve patient quality of life and delay the progression of the disease. In the future, precise diagnosis on the basis of clinical manifestation and genetic testing will become the gold standard for the diagnosis of hereditary eye diseases and syndromes. Finally, our results further increase the spectrum of WFS1 mutations by adding four novel variants to the limited data available in the Chinese population.