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Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: The aim of this study was to examine ethnicity-specific associations between type 2 diabetes mellitus and the risk of a cardiovascular disease (CVD) event as well as risk of specific CVD phenotypes in England., Methods: We obtained data from the Clinical Practice Research Datalink for adults with and without type 2 diabetes mellitus diagnosed 2000-2006. The outcome was the first CVD event during 2007-2017 and the following components: aortic aneurysm, cerebrovascular accidents, heart failure, myocardial infarction, peripheral vascular disease and other CVD-related conditions. Flexible parametric survival models were used to estimate ethnicity-specific adjusted hazard ratios., Results: A total of 734,543 people with and without type 2 diabetes mellitus (29,847; 4.1%) were included; most were of white ethnicity (93.0% with and 92.3% without type 2 diabetes mellitus) followed by South Asian (3.2 and 4.6%). During a median follow-up period of 11.0 years, 67,218 events occurred (6,156 in individuals with type 2 diabetes mellitus). Type 2 diabetes mellitus was associated with a small increase in CVD events (adjusted hazard ratio 1.06, 95% confidence interval 1.02-1.09) in individuals of white ethnicity; whereas the adjusted hazard ratios were considerably higher in individuals of South Asian ethnicity (1.28, 95% confidence interval 1.09-1.51), primarily due to an increased risk of myocardial infarction (1.53, 95% confidence interval 1.08-2.18)., Conclusions: Despite universal access to healthcare, there are large disparities in CVD outcomes in people with and without type 2 diabetes mellitus. Other non-traditional risk factors might play a role in the higher CVD risk associated with type 2 diabetes mellitus in individuals of South Asian ethnicity., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: The growth differentiation factor 5 (GDF5) gene regulates the growth of neuronal axons and dendrites and plays a role in the inflammatory response and tissue damage. The gene may also be associated with chronic postsurgical pain. This study aimed to reveal the relationship between SNPs in the GDF5 gene and orthopedic chronic postsurgical pain in Han Chinese population based on a case-control study., Methods: We genotyped 8 SNPs within GDF5 gene in 1048 surgical patients with chronic postsurgical pain as the case group and 2062 surgical patients who were pain free as the control group. SNP and haplotypic analyses were performed, and stratified analyses were conducted to determine the correlations between significant SNPs and clinical characteristics., Results: Only rs143384 in the 5'UTR of GDF5 was identified as significantly associated with increased susceptibility to chronic postsurgical pain, and the risk of A allele carriers was increased approximately 1.35-fold compared with that of G allele carriers. Haplotypes AGG and GGG in the LD block rs143384-rs224335-rs739329 also showed similar association patterns. Furthermore, we found that rs143384 was significantly correlated with chronic postsurgical pain in the subgroup aged ≤ 61 years, subgroup with a BMI ≤ 26, subgroup with no-smoking or no pain history, and subgroup with a drinking history., Conclusion: Our study provided supportive evidence that genetic variations in the GDF5 gene are potential genetic factors that can increase the risk of chronic postsurgical pain in the Han Chinese population, but further research is necessary to elucidate the underlying mechanism.

Aims: To investigate the progression pattern of diffuse chorioretinal atrophy (DCA) among Chinese participants with high myopia., Methods: This is a longitudinal, non-interventional study. Participants with high myopia, defined as ≤-6 diopters spherical power, were included and followed up for 4 years, and underwent cycloplegic autorefraction, best-corrected visual acuity (BCVA) and fundus photography examinations. Newly established DCA, enlargement of existing DCA and development of other lesions of myopic maculopathy were regarded as DCA progression., Results: Of the 484 participants with a mean age of 21.5±12.7 years (range, 6.8-69.7 years), 68 eyes (14.0%) showed DCA progression, with 88 lesion changes. The first appearance of DCA was identified in 21 eyes (23.9%). Of 88 eyes with DCA at baseline, 47 eyes (53.4%) showed progression, with 67 lesion changes, including 45 eyes (67.2%) with enlargement of DCA, 17 (25.3%) with a first appearance of lacquer cracks, 4 (6.0%) with development of patchy chorioretinal atrophy and 1 (1.5%) with increased numbers of lacquer cracks. Longer axial length (p<0.001), baseline DCA (p=0.005) and baseline DCA closer to the fovea (p=0.013) predicted DCA progression. Eyes had poorer BCVA at the follow-up if DCA was enlarging (p<0.001) or DCA was closer to the fovea at baseline (p=0.028) after adjusting for age,gender and cataract., Conclusion: Approximately half of the participants with DCA had progression over a 4-year follow-up. Enlargement and newly developed DCA were common progression patterns. Larger areas of DCA and foveal involvement with DCA could be indicators of a worse BCVA later., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

East Asia, geographically extending to the Pamir Plateau in the west, to the Himalayan Mountains in the southwest, to Lake Baikal in the north and to the South China Sea in the south, harbors a variety of people, cultures, and languages. To reconstruct the natural history of East Asians is a mission of multiple disciplines, including genetics, archaeology, linguistics, and ethnology. Geneticists confirm the recent African origin of modern East Asians. Anatomically modern humans arose in Africa and immigrated into East Asia via a southern route approximately 50,000 years ago. Following the end of the Last Glacial Maximum approximately 12,000 years ago, rice and millet were domesticated in the south and north of East Asia, respectively, which allowed human populations to expand and linguistic families and ethnic groups to develop. These Neolithic populations produced a strong relation between the present genetic structures and linguistic families. The expansion of the Hongshan people from northeastern China relocated most of the ethnic populations on a large scale approximately 5300 years ago. Most of the ethnic groups migrated to remote regions, producing genetic structure differences between the edge and center of East Asia. In central China, pronounced population admixture occurred and accelerated over time, which subsequently formed the Han Chinese population and eventually the Chinese civilization. Population migration between the north and the south throughout history has left a smooth gradient in north-south changes in genetic structure. Observation of the process of shaping the genetic structure of East Asians may help in understanding the global natural history of modern humans.

Rationale: Multiple endocrine neoplasia 2A (MEN2A) is a rare autosomal-dominant genetic syndrome, frequently misdiagnosed or neglected clinically, resulting in delayed therapy to patients., Patient Concerns: A 47-year-old Chinese male patient underwent laparoscopic right adrenal tumorectomy, and postoperative pathology confirmed the tumor as pheochromocytoma (PHEO). He was readmitted to the department of endocrinology and metabolism due to constant increase in carcinoembryonic antigen (CEA) at 5 months after the operation., Diagnosis: The patient was confirmed with medullary thyroid carcinoma (MTC), multiple neck lymph node metastasis, and pituitary microadenoma. The p.Cys611Tyr (c.1832G>A, C611Y) mutation was detected. Therefore, he was diagnosed with MEN2A., Interventions: He underwent total thyroidectomy. The gene-sequencing analysis of his family was conducted, and the C611Y mutation was detected in his daughter., Outcomes: The level of carcinoembryonic antigen decreased significantly after thyroidectomy in this patient. Long-term follow-up management was conducted. Elevated serum calcitonin and bilateral thyroid nodules were found in his 13-year-old daughter. Thus, MEN2A was highly suspected and she was suggested to undergo total thyroidectomy., Conclusion: Patients with MEN2A should be screened regularly and managed by a multidisciplinary team., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background : Mutations in the RCC1 and BTB domain-containing protein 1 ( RCBTB1 ) gene have been implicated in a rare form of retinal dystrophy. Herein, we report the clinical features of a 45-year-old Singaporean-Chinese female and her presymptomatic sibling, who each possesses compound heterozygous mutations in RCBTB1 . Expression of RCBTB1 in patient-derived cells was evaluated. Materials and Methods : The natural history was documented by a series of ophthalmic examinations including electroretinography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, visual field, microperimetry, and adaptive optics retinal imaging. Patient DNA was genetically analysed using a 537-gene Next Generation Sequencing panel and targeted Sanger sequencing. Expression of RCBTB1 in lymphocytes, fibroblasts, and induced pluripotent stem cells (iPSC) derived from the proband and healthy controls was characterized by quantitative PCR, Sanger sequencing, and western blotting. Results : The proband presented with left visual distortion at age 40 due to extrafoveal chorioretinal atrophy. Atrophy expanded at 1.3 (OD) and 1.0 (OS) mm 2 /year. Total macular volume declined by 0.09 (OD) and 0.13 (OS) mm 3 /year. Microperimetry demonstrated enlarging scotoma in both eyes. Generalised cone dysfunction was demonstrated by electroretinography. A retinal dystrophy panel testing revealed biallelic frameshifting mutations, c.170delG (p.Gly57Glufs*12) and c.707delA (p.Asn236Thrfs*11) in RCBTB1 . The level of RCBTB1 mRNA expression was reduced in patient-derived lymphocytes compared to controls. RCBTB1 protein was detected in control fibroblasts and iPSC but was absent in patient-derived cells. Conclusions : Atrophy expansion rate and macular volume change are feasible endpoints for monitoring RCBTB1 -associated retinopathy. We provide further functional evidence of pathogenicity for two disease-causing variants using patient-derived iPSCs.

Background: Accurate estimation of food portion sizes remains an important challenge in dietary data collection. The present study aimed to develop a food atlas with adequate visual reference to improve the accuracy of dietary surveys in China., Methods: A food atlas for dietary surveys in China was developed using three visual reference systems, namely, regularly placed food portions, the two-dimensional background coordinates and common objects known in daily life. The atlas was validated by estimating a meal before and after using the food atlas, and differences in weight estimation were compared using a paired t-test. In total, 50 college students participated in the study., Results: After determination of food varieties; design of the food display; purchase, processing, cooking and weighing of food; photographing food; post-image processing and data processing, a total of 799 pictures of 303 types of food and two types of tableware were produced. The mean value of food weight estimated with the atlas was closer to the actual weight, and the variation range of these values was smaller and more stable than that estimated without the atlas. The differences estimated before and after using the atlas for all foods were significant (P < 0.05). Comparing the differences in weight before using the atlas, the error ranges of food samples were reduced., Conclusions: A food atlas has been developed for a retrospective dietary survey in China, which can be used to enable a better understanding of nutritional adequacy in the Chinese population., (© 2021 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.)

Cambodia harbours a variety of human aboriginal populations that have scarcely been studied in terms of genetic diversity of entire mitochondrial genomes. Here we present the matrilineal gene pool of 299 Cambodian refugees from three different ethnic groups (Cham, Khmer, and Khmer Loeu) deriving from 16 Cambodian districts. After establishing a DNA-saving high-throughput strategy for mitochondrial whole-genome Sanger sequencing, a HaploGrep based workflow was used for quality control, haplogroup classification and phylogenetic reconstruction. The application of diverse phylogenetic algorithms revealed an exciting picture of the genetic diversity of Cambodia, especially in relation to populations from Southeast Asia and from the whole world. A total of 224 unique haplotypes were identified, which were mostly classified under haplogroups B5a1, F1a1, or categorized as newly defined basal haplogroups or basal sub-branches of R, N and M clades. The presence of autochthonous maternal lineages could be confirmed as reported in previous studies. The exceptional homogeneity observed between and within the three investigated Cambodian ethnic groups indicates genetic isolation of the whole population. Between ethnicities, genetic barriers were not detected. The mtDNA data presented here increases the phylogenetic resolution in Cambodia significantly, thereby highlighting the need for an update of the current human mtDNA phylogeny.

The uniqueness and reliability of frontal sinuses for personal identification have gained wide recognition in forensics. However, few studies have assessed the usefulness of a three-dimensional (3D) model of the frontal sinus for human identification. This study aimed to develop standardized techniques to classify the frontal sinus according to its 3D morphological metrics and discover the usefulness of the 3D frontal sinus model in identification of Chinese Han population. One hundred and ninety-six computed tomography (CT) scans of patients older than 20 years (84 males and 112 females) were collected. A 3D frontal sinus digital model was segmented using Dolphin Imaging software. The following morphological metrics of the 3D frontal sinus were used to develop the coding system: bilateral or unilateral, spatial relationships of the two sides, number of septations, superior volume side, the shape of the 3D model of each side, shape of the medial surface and frontal ostium on each side, number of accessory septations on each side, number of supra-orbital cells of the medial surface and lateral surface on each side, and number of the arcades on each side. The new coding system accurately identified all of our research individuals. This study discovered a number of individual variations in the 3D frontal sinus morphology patterns. A coding system, which is based on these morphological patterns, exposes the morphological variants of frontal sinuses and presents the usefulness of 3D frontal sinus model for human identification.

Y-chromosome haplotypes of 527 non-related males (176 Han, 186 Tibetan, and 165 Yi) in the Tibetan-Yi corridor were analyzed using SureID® PathFinder Plus. In the populations of Han, Tibetans, and Yi, the haplotype diversity was 0.9989, 0.9981, and 0.9993, respectively, and the discrimination capacity was 0.9148, 0.8925, and 0.9576, respectively. Phylogenetic relationships among 12 studied ethnic groups and 7 other ethnic groups in the Tibetan-Yi corridor were investigated. Both multi-dimensional scaling analysis and phylogenetic reconstructions indicated that Tibetans appeared separated from the Han and Yi ethnic groups in the Tibetan-Yi corridor. Their genetic homogeneity or heterogeneity has not entirely been affected by their geographical distance and linguistic origin.

Purpose: To identify prognostic factors for axial length (AL) elongation and incidence of posterior staphyloma (PS) in adult Japanese patients with high myopia., Design: Retrospective, observational cohort study., Methods: Six-year follow-up data for 345 patients (620 eyes with AL ≥ 26.5 mm and spherical equivalent [SE] ≤- 8.00 diopters) admitted to the Tokyo Medical and Dental University Hospital from 2007 to 2017 were analyzed retrospectively. Main outcome measures were change in AL from baseline, factors associated with AL, categorization of eyes with high myopia, factors associated with incidence of PS, and impact of PS on myopic maculopathy and visual function., Results: The mean annual increase in AL was 0.03 mm. Presence of optic nerve disc conus (P = .025), steeper corneal curvature, lower SE, and decreased choroidal thickness (CT) (all P < .001) were associated with increased AL in univariate and multivariate analyses. Younger age (P = .003) and no use of intraocular pressure-lowering medications (P = .046) were associated with increased AL. Eyes with high myopia were categorized using factor analysis as associated with glaucoma, severe pathologic myopia, and mild-to-moderate pathologic myopia. Older age, increased AL, glaucoma, and choroidal thinning (all P ≤ .001) were identified as significant risk factors for the incidence of PS in univariate and/or multivariate analyses. Incidence of PS was a precursor for myopic maculopathy and visual field defects., Conclusions: Optic nerve disc conus, steeper corneal curvature, lower SE, decreased CT, and no use of intraocular pressure-lowering medications were prognostic factors for increased AL. Older age, increased AL, glaucoma, and decreased CT were prognostic factors for PS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To evaluate the applicability of 23 autosomal STR loci (D10S1248, D11S4463, D12ATA63, D14S1434, D17S1301, D18S853, D1GATA113, D1S1627, D6S1017, D20S1082, D20S482, D17S974, D22S1045, D1S1677, D2S1776, D2S441, D3S4529, D4S2408, D9S1122D5S2500, D6S474, D18S51, D9S2157) included in DNA Typer™ 25 Kit for individual identification and parentage testing, allele frequencies and forensic efficiency parameters were first obtained from healthy, unrelated 506 Chongqing Tujia individuals. A total of 1012 alleles were identified in 23 STR loci, and allele frequencies ranged from 0.001 to 0.5761. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) of the 23 STR loci were 0.999999999999999999999753 and 0.99999967, respectively. These results suggested that 23 autosomal STR loci could be used as an effective tool for forensic application in Chongqing Tujia population. Comprehensive comparisons were conducted based on the analysis of genetic distance, principal component analysis (PCA), multidimensional scaling plot (MDS), and phylogenetic tree to explore the interpopulation genetic relationship. Our results revealed that Chongqing Tujia keeps the more relatively genetic similarity with Hunan Han, Hubei Tujia, and Sichuan Han, which could be interpreted by that those populations were originated from the same ethnic ancestor or genetic communication were happened in adjacent areas.

The MiSeq® FGX Forensic system and the HID-Ion AmpliSeq Panel were previously developed for massively parallel sequencing (MPS) for forensic casework. Among the three major sequencing platforms, BGISEQ-500 TM , which is based on multiple PCRs, is still lacking in forensics. Here, a novel forensic panel was constructed to detect 186 single-nucleotide polymorphisms (SNPs) and 123 short tandem repeats (STRs) with MPS technology on the BGISEQ-500™ platform. First, the library preparation, sequencing process, and data analysis were performed, focusing on the average depth of coverage and heterozygote balance. We calculated the allelic frequencies and forensic parameters of STR and SNP loci in 73 unrelated Chinese Han individuals. In addition, performance was evaluated with accuracy, uniformity, sensitivity, PCR inhibitor, repeatability and reproducibility, mixtures, degraded samples, case-type samples, and pedigree analyses. The results showed that 100% accurate and concordant genotypes can be obtained, and the loci with an abundance in the interquartile range accounted for 92.90% of the total, suggesting reliable uniformity in this panel. We obtained a locus detection rate that was higher than 98.78% from 78 pg of input DNA, and the optimal amount was 1.25-10 ng. The maximum concentrations of hematin and humic acid were 200 and 100 μM, respectively (the ratios of detected loci were 96.52% and 92.41%), in this panel. As a mixture, compared with those of SNPs, minor-contributor alleles of STRs could be detected at higher levels. For the degraded sample, the ratio of detected loci was 98.41%, and most profiles from case-type samples were not significantly different in abundance in our studies. As a whole, this panel showed high-performance, reliable, robust, repeatable, and reproducible results, which are sufficient for paternity testing, individual identification, and use for potentially degraded samples in forensic science.

China is a populous country but lacks epidemiological data on keratoconus (KC). The present study aimed to investigate the clinical data, demographic data, and visual function (VF) data of KC patients in Central China. A total of 524 KC eyes in 307 KC patients (217 bilateral and 90 unilateral) from Henan Eye Hospital were included in the current study. Demographic and VF data were assessed with questionnaires administered by well-trained staff during face-to-face interviews. Visual acuity value was examined by a qualified optometrist, and the clinical data were measured by professional clinicians. The distributions of sex, residence and education level of KC patients were compared by Chi-square tests, and the ratios of people wearing glasses and rigid gas permeable (RGP) lenses were compared by McNemar tests. General linear models/Chi-squared tests were used to compare the clinical and demographic data according to KC severity. Spearman's correlation analysis was used to test the associations between the data and KC severity. The mean age at diagnosis was 20.98 ± 6.06 years, and males had a higher ratio of KC than females (P < 0.001). Patients in rural areas had a higher rate of KC than those in urban areas (P = 0.039), and the proportion of KC patients with a higher education level (above high school) was high (P < 0.001). A total of 68.40% of the patients reported eye rubbing and 3.52% had a positive family history. The percentage of people wearing glasses was higher than that of patients wearing RGP lenses (P < 0.001). The total VF score of KC patients was 69.35 ± 15.25. The thinnest corneal thickness (TCT) and stiffness parameter at the first applanation (SP-A1) values were inversely correlated with KC severity (P < 0.05). The mean, steep, and max keratometry (Km, Ks and Kmax) values, the RGP lens use and keratoplasty were positively correlated with KC severity (all P < 0.05). The total VF score of the eye with better VA decreased as the severity increased (r = - 0.21, P = 0.002). The present study comprehensively describes various associated features of KC patients from a tertiary hospital in Central China, providing a reference for understanding the characteristics of KC patients in China.

Introduction: Renal involvement is seen in about 40-82% of systemic lupus erythematosus (SLE) Asian patients. The exact diagnosis and classification of lupus nephritis are important for treatment and prognosis. This study aimed to investigate the value of electron microscopy (EM) in the diagnosis and classification of lupus nephritis compared with light microscopy., Method: In this cross-sectional referral-center 16-year study of lupus nephritis, the final diagnosis was based on the EM study. Primary light microscopy findings were compared with EM diagnosis. Moreover, Immunofluorescence patterns distribution was assessed., Results: From 496 patients diagnosed with lupus nephritis based on EM, 225(45.4%) of patients were categorized in class IV, followed by 98(19.7%), 93(18.8%), 46(9.3%), and 14(2.8%) who were categorized into classes of II, III, V, and VI respectively. Only 1(0.2%) patient belonged to class I, and 19(3.8%) cases were diagnosed with mixed two classes. Using EM was essential for diagnosing 25.6% of cases taking the correct classification by light microscopy into account; however, disregarding correct classification, this could change to a 7.4% contribution rate of EM. The most common cause of misdiagnosis, disregarding incorrect classification, was inadequate or wrong tissue. Positive associations were detected between tubular atrophy and interstitial fibrosis of both electron and light microscopy with different classes (P < 0.001)., Conclusion: While light microscopy is highly accurate for diagnosing lupus nephritis regardless of correct classification, EM contributes substantially to the correct classification of lupus nephritis types.

Introduction: The study assessed whether self-reported height, weight and derived body mass index (BMI) can provide an accurate measure of anthropometric data in a multiethnic adult population in Singapore., Methods: Standardised anthropometric measurements were compared against the self-reported values from 5,132 adult residents in a cross-sectional, epidemiological survey. Discrepancies in self-reports from measurements were examined by comparing overall mean differences. Intraclass correlations, Cohen's kappa and Bland-Altman plots with limits of agreement, and sub-analysis by sex and ethnicity were also explored., Results: Data were obtained from 5,132 respondents. The mean age of respondents was 43.9 years. Overall, the height was overestimated (0.2cm), while there was an underestimation of weight (0.8kg) and derived BMI (0.4kg/m2). Women had a larger discrepancy in height (0.35cm, 95% confidence interval [CI] 0.22 to 0.49), weight (-0.95kg, 95% CI -1.11 to -0.79) and BMI (-0.49kg/m2, 95% CI -0.57 to -0.41) compared with men. Height reporting bias was highest among Indians (0.28cm, 95% CI 0.12 to 0.44) compared with Chinese and Malays, while weight (-1.32kg, 95% CI -1.53 to -1.11) and derived BMI (-0.57kg/m2, 95% CI -0.67 to -0.47) showed higher degrees of underreporting among Malays compared with Chinese and Indians. Substantially high self-reported versus measured values were obtained for intraclass correlations (0.96-0.99, P <0.001) and kappa (0.74). For BMI categories, good to excellent kappa agreement was observed (0.68-0.81, P <0.0001)., Conclusion: Self-reported anthropometric estimates can be used, particularly in large epidemiological studies. However, sufficient care is needed when evaluating data from Indians, Malays and women as there is likely an underestimation of obesity prevalence.

Purpose: To review the long-term outcomes of optical, therapeutic and tectonic forms of penetrating keratoplasty over a 20-year period in Asian eyes., Design: Prospective cohort study involving the Singapore Corneal Transplant Study (SCTS)., Methods: All penetrating keratoplasties (PK) performed at the Singapore National Eye Centre (SNEC) from January 1991 to December 2010 were analyzed using records from the computerized database of the SCTS. This database includes preoperative, intraoperative, and postoperative patient data and donor cornea data. Only primary grafts were included. Patient demographics, donor cornea source, indications for grafting, complications, graft survival rate, and causes of graft failure were analyzed., Results: A total of 1,206 primary PKs were performed. The mean age of the patients was 55 years (range: <1-101 years). The overall corneal graft survival rates at 1, 5, 10, 15, and 20 years were 91%, 66.8%, 55.4%, 52%, and 44%, respectively. For optical grafts, pseudophakic bullous keratopathy, postinfectious corneal scarring and thinning and keratoconus were the most common diagnoses. Graft survival for optical grafts was significantly better than therapeutic and tectonic grafts at all time points. Multivariate analysis suggested that a younger donor cornea age and higher donor endothelial cell count are associated with better long-term graft survival for optical grafts. Irreversible allograft rejection and late endothelial failure accounted for more than 60% of graft failures., Conclusions: Graft survival decreased over time from 91% at 1 year to 44% at 20 years' follow-up. Allograft rejection and late endothelial failure accounted for more than 60% of graft failures., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Recent studies have reported that lncRNA (long noncoding RNAs) antisense non-coding RNA in the INK4 locus (ANRIL) plays important roles in the development of atherosclerosis through regulating cell apoptosis, proliferation, and adhesion. GWAS (genome-wide association studies) identified common genetic variants within ANRIL could confer risk of ischemic stroke (IS) in southern Sweden., Methods: We performed a case-control study, including 567 IS patients and 552 healthy controls from unrelated northern Chinese Han population, aiming to explore the association between lncRNA ANRIL rs2383207, rs4977574 polymorphisms and the risk of IS. Subsequently we implemented a meta-analysis to further assess the relationship of these variants and the disease., Results: In our case-control study, no significant associations were observed in all models between above 2 polymorphisms and IS. Next in our subgroup analysis, we detected significant association between GA genotype of rs4977574 and the increased risk of LAA-IS (large-artery atherosclerotic ischemic stroke), similar elevated risk also appeared in the GG + GA genotype under the dominant model (P = .048, OR = 1.385, 95% CIs 1.002-1.914; P = .040, OR = 1.378, 95% CIs 1.015-1.872, respectively). As for rs2383207, negative results were obtained under all models and subgroups. Our meta-analysis showed a significant association between rs4977574 polymorphism and IS risk in allele model (G vs A P = .002, OR = 1.137, 95% CIs 1.048-1.234); with respect to rs2383207 polymorphism, no significant association between that and the risk of IS was detected under the dominant model (GA + AA vs GG, P = .061, OR = 0.923, 95% CIs 0.849-1.004), or recessive model (AA vs GA + GG, P = .656, OR = 0.972, 95% CIs 0.858-1.101), or allele model (A vs G, P = .326, OR = 0.952, 95% CIs 0.863-1.050). Likewise, no significant association between rs2383207 and IS was found in different stoke subtypes (P > .05)., Conclusions: Our findings indicated G allele of lncRNA ANRIL rs4977574 could increase the risk of IS, and the variant may be associated with susceptibility to LAA-IS in Chinese Han population., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The hill tribes of northern Thailand comprise nine officially recognized groups: the Austroasiatic-speaking (AA) Khmu, Htin and Lawa; the Hmong-Mien-speaking (HM) IuMien and Hmong; and the Sino-Tibetan-speaking (ST) Akha, Karen, Lahu and Lisu. Except the Lawa, the rest of the hill tribes migrated into their present habitats only very recently. The Thai hill tribes were of much interest to research groups focusing on study of cultural and genetic variation because of their unique languages and cultures. So far, there have been several genetic studies of the Thai hill tribes. However, complete forensic microsatellite database of the Thai hill tribes is still lacking. To construct such database, we newly generated 654 genotypes of 15 microsatellites commonly used in forensic investigation that belong to all the nine hill tribes and also non-hill tribe highlanders from northern Thailand. We also combined 329 genotypes from previous studies of northern Thai populations bringing to a total of 983 genotypes, which were then subjected to genetic structure and population relationships analyses. Our overall results indicated homogenous genetic structure within the HM- and Tai-Kadai (TK)-speaking groups, large genetic divergence of the HM-speaking Hmong but not IuMien from the other Thai groups, and genetic heterogeneity within the ST- and AA-speaking groups, reflecting different population interactions and admixtures. In addition to establishing genetic relationships within and among these populations, our finding, which provides a more complete picture of the forensic microsatellite database of the multiple Thai highland dwellers, would not only serve to expand and strengthen forensic investigation in Thailand, but would also benefit its neighboring countries of Laos and Myanmar, from which many of the Thai hill tribes originated and where large populations of these ethnic groups still reside.

Accumulating evidence suggests that epigenetics plays an important role in the etiology of schizophrenia. Here, we performed a methylome-wide association study (MWAS) of first-onset schizophrenia patients and controls from the Han Chinese population using microarray technology. The DNA methylation profiles revealed 4494 differentially methylated CpG sites. Gene ontology (GO) analysis showed that the functions of differentially methylated genes were primarily involved in enzymatic activity, cytoskeleton organization and cell adhesion, and the TNIK (encoding TRAF2- and NCK-interacting kinase) gene was enriched in most of these terms. By combining the MWAS results with those of previous genome-wide association studies (GWASs), we identified 72 candidate genes located in 49 human genome loci. Among the overlapping genes, the most significantly methylated CpG sites were in the transcriptional start site (TSS) 200 region (cg21413905, P unadjusted  = 3.20 × 10 -5 ) of TNIK. TNIK was listed in the top 50 differentially methylated loci. The results of pyrosequencing and TNIK mRNA expression were consistent with those of the microarray study. Bioinformatics analyses, dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) studies showed that TNIK interacted with genes associated with schizophrenia and NRF1 was identified as a novel transcription factor (TF) that binds to TNIK in its TSS200 region. Thus, the regulatory function of NRF1 may be influenced by the status of the methylated CpG site in this region. In summary, our study provides new insights into the epigenetic mechanisms that regulate schizophrenia. Studies of the functions of TNIK methylation should be performed in vitro and in vivo to provide a better understanding of the pathophysiology of schizophrenia., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: We sought to assess the effects of exposure to secondhand smoke (SHS) on peripapillary retinal nerve fiber layer (p-RNFL) thickness in children., Design: Cross-sectional study., Methods: Children 6-8 years of age were consecutively recruited from the population-based Hong Kong Children Eye Study. All participants received comprehensive ophthalmic examinations and p-RNFL thickness was measured by spectral-domain optical coherence tomography. SHS data were derived from a validated questionnaire. Associations between p-RNFL thickness and SHS exposure status, number of smokers in the family, and quantity of smoking in the family were determined by multivariate linear regression after adjusting for potential confounders., Results: Among the Hong Kong Children Eye Study cohort (n = 3,103), approximately one-third of children were exposed to SHS (35.4%, n = 1,097). Compared to those without exposure to SHS, children exposed to SHS had similar age (P = .83), gender (P = .17), body mass index (P = .44), birth weight (P = .23), and axial length (P = .34), but had lower family income (P < .001) and lower parental education level (P < .001). After adjusting for all the above factors, exposure to SHS was associated with a thinner global p-RNFL by 4.4 μm (P < .001). Reduced p-RNFL was also associated with increased numbers of smokers in the family (β = -3.40, P < .001) and increased quantity of SHS (β = -0.22, P < .001)., Conclusions: Exposure to SHS in children was associated with a thinner p-RNFL. A thinner p-RNFL may increase the risk of irreversible visual impairment in the future. Our results provide evidence to recommend that children avoid exposure to SHS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: This study aimed to evaluate the prevalence of peripheral vestibular disorders in an Asian population of predominantly Han Chinese ethnicity., Study Design: Cross-sectional study., Methods: Patients with a peripheral vertigo disorder were identified from the Taiwan Health Insurance Research Database, a database of all medical claims of a randomly selected, population-representative sample of 2 million enrollees of Taiwan's National Health Insurance system covering over 99% of Taiwan's citizens. In 2016, 59,986 patients received a diagnosis of peripheral vestibular disorders in Taiwan. We calculated the population-wide prevalence rates of peripheral vestibular disorders in 2016 by sex and age group (20 to 24, 25 to 29, 30 to 34, 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, 60 to 64, 65 to 69, and ≥ 70 years) stratified into five urbanization levels., Results: The prevalence rate of peripheral vestibular disorders was 2,833.4 per 100,000 population during the year. Prevalence of Meniere's disease was 70.4 per 100,000, benign paroxysmal positional vertigo, 446.4, vestibular neuritis 307.2, and other or unspecified peripheral vestibular dizziness, 2,009.5 per 100,000. Prevalence rates steadily increased with age for every type of peripheral vestibular disorder, and were higher among females compared to males. The female-to-male gender ratios were 1.84, 1.89, and 1.93 for Meniere's disease, vestibular neuritis, and other peripheral vestibular dizziness, respectively. Counties with the lowest urbanization level had the highest prevalence rates of all types of peripheral vestibular disorders except vestibular neuritis., Conclusions: Results showed that peripheral vestibular disorders are common in Taiwan, increase with age, are predominantly female, and show higher prevalence in rural areas., Level of Evidence: 2b Laryngoscope, 131:639-643, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Visual impairment (VI) can have a detrimental impact on vision-related quality of life (VRQoL), but it is still unclear how this relationship varies with age across the VI spectrum. We determined the age-stratified, cross-sectional, and longitudinal associations between VI severity and VRQoL., Design: The baseline and follow-up Singapore Chinese Eye Studies (SCES-1/-2; 2009-2011 and 2015-2017)., Participants: A total of 3068 SCES-1 participants (mean age [standard deviation {SD}]: 59.5 [9.8] years; 50.2% female) and 1919 SCES-2 participants (mean age [SD]: 56.8 [8.3] years; 49.9% female)., Methods: Visual impairment was defined as visual acuity (VA) of > 0.3 logarithm of the minimum angle of resolution (logMAR) units; VI severity as mild-moderate (logMAR scores less than the median of all individuals with VI) and severe (logMAR scores median or greater); and VI incidence as VI absence at baseline, but evident at follow-up. Age was stratified into 40 to 49 years, 50 to 64 years, and ≥65 years., Main Outcome Measures: Rasch-transformed scores from the 32-item Impact of Visual Impairment (IVI) questionnaire were used to measure the "Reading," "Mobility," and "Emotional" domains of VRQoL. Multiple linear regression models determined the age-stratified associations of prevalent and incident VI with all 3 VRQoL outcomes, adjusted for potential confounders., Results: Of the 807 persons with prevalent VI, 55.9% had mild-moderate and 44.1% had severe VI. Compared with no VI, age-stratified analyses showed that VRQoL decrements were significant only in the older age groups (mild-moderate VI: 6.2% and 8.1% reduction in Mobility and Reading scores in those aged ≥ 65 years; severe VI: 8.5% to 13.4% reductions in the 3 VRQoL scores in those aged ≥ 50 years). This interaction with older age became more pronounced with incident VI (N = 168), where decrements in all 3 VRQoL domains were evident only in those aged ≥65 years compared with persons without incident VI., Conclusions: Our results suggest that the VI-VRQoL associations are driven mainly by older individuals aged ≥65 years, highlighting the need for effective regular screening and early intervention modalities to prevent the presence and onset of VI, and subsequent VRQoL declines, in these individuals., (Copyright © 2020 American Academy of Ophthalmology. All rights reserved.)

Liangshan Yi Autonomous Prefecture locates at the south of Sichuan, China, and this area has the largest population of Yi ethnic nationally. In order to study the population data of Y-STRs of this area and contribute to the worldwide Y-STR database, we genotyped 628 unrelated individuals using commercially available Goldeneye® DNA ID 27Y system. Gene diversity (GD) values and haplotype diversity (HD) were calculated. Population comparison results showed that Liangshan Yi population was significantly differently from other populations.

Purpose: To evaluate the changes of corneal biomechanics and the intraocular pressure during pregnancy in a Chinese healthy female population., Methods: A total of 222 unrelated Chinese females were recruited: 52 non-pregnant, 15 pregnant in the first trimester, 68 pregnant in the second trimester, and 87 pregnant in the third trimester. The intraocular pressure and corneal biomechanical parameters, including corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, corneal hysteresis, and corneal resistance factor, were measured by an Ocular Response Analyzer G3. Central corneal thickness was measured by Lenstar (LS900)., Results: Corneal hysteresis and corneal resistance factor were significantly higher in pregnant women at the second and third trimesters. Corneal-compensated intraocular pressure was lower in women at the third trimester of pregnancy ( p  = 0.023), but the difference became insignificant after adjustment for corneal hysteresis. Central corneal thickness was marginally higher in pregnant women than non-pregnant women ( p  = 0.032). There was a negative correlation between corneal-compensated intraocular pressure and corneal hysteresis ( r  = -0.337, p  < 0.001) and a positive correlation between central corneal thickness and corneal hysteresis ( r  = 0.711, p  < 0.0001). After adjustment for corneal-compensated intraocular pressure, corneal hysteresis remained significantly higher in the second and third trimesters of pregnant women than non-pregnant women ( p  = 0.031, p  = 0.005)., Conclusion: This study revealed a significant increase in corneal hysteresis and corneal resistance factor in the second and third trimesters. The increase of corneal hysteresis was independent of corneal-compensated intraocular pressure, indicating pregnant females have unique characteristics in corneal-compensated intraocular pressure and corneal biomechanical properties that may be related to glaucoma and corneal ectatic diseases in pregnancy.

Past research on Singapore English (SgE) has shown that there are specific segmental and prosodic patterns that are unique to the three major ethnic groups, Chinese, Malay, and Indian in Singapore. These features have been highlighted as the "stereotypical" ethnic markers of SgE speakers, assuming substrate influence from the speakers' "ethnic" languages (Mandarin, Malay, and Tamil). However, recent research suggests that Singaporeans are becoming increasingly English dominant and has challenged the position of the ethnic languages as true "mother tongues" of Singaporeans. Hence, this study seeks to question if such "stereotypical" ethnic features exist, and if so, the extent to which a less dominant ethnic language would affect the phonology of speakers' English. This study looks specifically at the production of consonants /f/, /θ/, /t/, /v/, and /w/ as salient segmental features in SgE. Participants' phonetic behavior of /θ/, which was produced similarly across the three ethnic groups, disputed substrate influence. Tamil speakers were the most disparate, particularly with the /v/-/w/ contrast production. However, these deviations were often sporadic phonetic changes, which scarcely reflect robust speech patterns in the community. As a result, consonantal production in SgE is found to be largely independent of substrate influence and relatively uniform across the three ethnicities. The homogeneity observed in this study sheds light on bilinguals' acquisition of sounds, and it also provides phonological evidence toward the understanding of the evolutionary process of postcolonial Englishes.

Background: The effect of modest alcohol intake on prevalence of significant hepatic steatosis and severity of liver disease in patients with type 2 diabetes mellitus (T2DM) is unclear., Methods: This is a cross-sectional study on T2DM patients. Modest alcohol intake was defined as alcohol intake ≤ 21 units/week in men and ≤ 14 units/week in women. Significant hepatic steatosis was diagnosed on the basis of controlled attenuation parameter > 263 dB/m, while advanced fibrosis was diagnosed on the basis of liver stiffness measurement ≥ 9.6 kPa using M probe or ≥ 9.3 kPa using XL probe. Patients with liver stiffness measurement ≥ 8.0 kPa were offered liver biopsy., Results: Five hundred fifty-seven patients underwent transient elastography, and 71 patients underwent liver biopsy. The prevalence of modest drinking was 16.5%. Modest drinking was equally prevalent among ethnic Indians and Chinese at 22.9% and 23.3%, respectively, but uncommon among ethnic Malays at 1.7%. Modest drinkers were more likely to be male, smoked, and had significantly lower glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol, alkaline phosphatase, and platelet count. There was no significant difference in the prevalence of significant hepatic steatosis or advanced fibrosis based on transient elastography and steatohepatitis or advanced fibrosis between modest drinkers and nondrinkers. The prevalence of significant hepatic steatosis was higher among ethnic Malays and Indians compared with ethnic Chinese, but the Chinese did not have a lower prevalence of more severe liver disease., Conclusion: Modest alcohol intake is not associated with higher prevalence of significant hepatic steatosis or more severe liver disease among patients with T2DM., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood., Objective: To explore the genetic basis of BD in the Han Chinese population., Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020., Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association., Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956)., Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Background: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis , is a major public health concern. Chemokines and their receptors, such as RANTES, CXCR3, and CCR5, have been reported to play important roles in cell activation and migration in immune responses against TB infection., Methods: To understand the correlations involving CCR5 gene variations, M. tuberculosis infection, and TB disease progression, a case-control study comprising 450 patients with TB and 306 healthy controls from a Chinese Han population was conducted, along with the detection of polymorphisms in the CCR5 promoter using a sequencing method., Results: After adjustment for age and gender, the results of logistic analysis indicated that the frequency of rs2734648-G was significantly higher in the TB patient group ( P = 0.002, OR = 1.38, 95% CI: 1.123-1.696); meanwhile, rs2734648-GG showed notable susceptibility to TB ( P = 6.32E-06, OR = 2.173, 95% CI: 1.546-3.056 in a recessive model). The genotypic frequency of rs1799987 also varied between the TB and control groups ( P = 0.008). In stratified analysis, rs2734648-GG significantly increased susceptibility to pulmonary TB in a recessive model ( P < 0.0001, OR = 2.382, 95% CI: 1.663-3.413), and the rs2734648-G allele significantly increased susceptibility to TB recurrence in a dominant model ( P = 0.0032, OR = 1.936, 95% CI: 1.221-3.068), whereas rs1799987-AA was associated with susceptibility to pulmonary TB ( P = 0.0078, OR = 1.678, 95% CI: 1.141-2.495 in a recessive model) but not with extra-pulmonary TB and TB recurrence. A haplotype constructed with the major alleles of the eight SNPs in the CCR5 promoter (rs2227010-rs2856758-rs2734648-rs1799987-rs1799988-rs41469351-rs1800023-rs1800024: A-A-G-G-T-C-G-C) exhibited extraordinarily increased risk of susceptibility to TB and pulmonary TB ( P = 6.33E-11, OR = 24.887, 95% CI: 6.081-101.841)., Conclusion: In conclusion, CCR5 promoter polymorphisms were found to be associated with pulmonary TB and TB progression in Chinese Han people., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liu, Wang, Zhang, Yao, Zhang and Shi.)

Rationale: Pulmonary artery intimal sarcoma is a rare tumor with exceptionally high mortality and easily misdiagnosed as pulmonary thromboembolism pulmonary thromboembolism (PTE) due to the nonspecific clinical presentation and symptom. Misdiagnosis or untimely diagnosis makes the disease progress to an advanced stage and eventually leads to a poor prognosis., Patient Concerns: A 37-year-old Chinese female presented with chest tightness and dyspnea for 3 months. Echocardiography and chest computed tomography revealed an intraluminal obstruction of the pulmonary arteries. Tests of serum tumor makers showed slight elevation for carbohydrate antigen-125, and α-fetoprotein. PTE was suspected according to the radiological and laboratory findings., Diagnosis: Microscopic findings of the presumed thrombus showed prominent myxoid and edematous background with atypical spindled cells and curvilinear vascularity. Immunohistochemical staining demonstrated that the atypical spindled cells were positive for vimentin but negative for CK, S100, SMA, desmin, CD68, STAT6, CD34, β-catenin, ALK-p80, p53, and MDM2. According to the radiological and pathological findings, the diagnosis of fibrosarcoma of pulmonary artery was made., Interventions: The patient underwent surgical resection and the mass was excised as completely as possible., Outcome: Follow-up information showed no evidence of recurrence or metastasis after 3 months postresection., Lessons: Because of the low incidence rate, nonspecific clinical symptoms, and radiological findings, primary fibrosarcoma of the pulmonary artery is commonly misdiagnosed as PTE. Pathological examination is necessary to confirm the diagnosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To explore the impact of puberty on refractive development and its interaction with outdoor time in children and adolescents., Methods: In this 2-year observational study, students aged 7-13 years were selected with cluster sampling. All participants underwent cycloplegic refraction and axial length measurements once every year. Information of related factors was acquired through proper questionnaire or inquiry. The level of testosterone/estradiol was detected from the saliva of the subjects using the ELISA kit. Multiple linear regression and generalised estimating equation (GEE) were used to analyse the relationship among puberty, outdoor activities and refractive indicators., Results: A total of 776 children and adolescents were included, with an average baseline age of 9.64±1.54 years and 53.6% boys. There were 350 myopes (55.2% of the 634 cyclopleged subjects) at baseline. There was a significant difference in the mean axial length changes and outdoor time among different puberty groups (for axial length: p=0.017, for outdoor time: p=0.015). Myopic parents, less outdoor time and more changes in estradiol were associated with greater changes in axial length and spherical equivalent (SE) (axial length changes: parental myopia β =0.230, outdoor time β =-0.250, changes in estradiol β =0.261; SE changes: parental myopia β =-0.267, outdoor time β =0.256, changes in estradiol β =-0.297). In the GEE model, the interaction between outdoor time and puberty was significantly associated with axial length (p=0.024, β =1.199)., Conclusions: This study implies puberty may play a regulating role on the relationship between outdoor time and refractive development among Chinese children and adolescents, which provides clues for in-depth mechanism interpretation and efficient intervention strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Identification of ancestry-specific pathogenic variants is imperative for diagnostic, treatment, management and prevention strategies, and to understand penetrance/modifiers on risk. Our study aimed to determine the clinical significance of a recurrent BRCA1 c.442-22&#95;442-13del variant of unknown significance identified among 13 carriers from six Chinese families, all with a significant history of breast and/or ovarian cancer. We further aimed to establish whether this was due to a founder effect and explore its origins. Haplotype analysis, using nine microsatellite markers encompassing 2.5 megabase pairs around the BRCA1 locus, identified a common haploblock specific to the variant carriers, confirming a founder effect. Variant age was estimated to date back 77.9 generations to 69 bc using the Gamma approach. On principal component analysis using single nucleotide polymorphisms merged with 1000 Genomes dataset, variant carriers were observed to overlap predominantly with the southern Han Chinese population. To determine pathogenicity of the variant, we assessed the functional effect on RAD51 foci formation as well as replication fork stability upon induction of DNA damage and observed an impaired DNA repair response associated with the variant. In summary, we identified an ancient Chinese founder mutation dating back 77.9 generations, possibly common among individuals of southern Han Chinese descent. Using evidence from phenotypic/family history studies, segregation analysis and functional characterization, the BRCA1 variant was reclassified from uncertain significance to pathogenic., (© 2020 Union for International Cancer Control.)

A 54-year-old Japanese woman developed simultaneous abdominal distension and bilateral leg edema. Her medical history and results of periodic medical check-up were unremarkable. Blood tests revealed severe hypoproteinemia and acute kidney injury, and urinalysis revealed 4+ proteinuria and 2+ hematuria. Abdominal computed tomography revealed a large intra-abdominal mass with fat tissue density. She underwent emergency tumor excision, splenectomy, and distal pancreatectomy. However, hypoproteinemia and acute kidney injury worsened. Therefore, she was transferred to the nephrology division for confirmation of diagnosis and for treatment of acute kidney injury and nephrotic syndrome. We conducted percutaneous kidney biopsy and diagnosed minimal change disease (MCD). Intravenous prednisolone was started, and heavy proteinuria and systemic edema were gradually alleviated. She achieved complete remission 2 months later, and oral prednisolone was tapered. Histopathological diagnosis of abdominal tumor was dedifferentiated liposarcoma of retroperitoneal origin. Immunohistochemical staining revealed strong expression of vascular endothelial growth factor in the tumor cells in the dedifferentiated component. Currently, her clinical course is stable without recurrence of liposarcoma and nephrotic syndrome. MCD develops in patients with Hodgkin's lymphoma, solid organ cancers, hematological malignancies, and thymoma, whereas concurrent MCD and liposarcoma are rare. Remission of nephrotic syndrome and normalized kidney function induced by steroid therapy are important for better management of patients with malignancy.

Importance: Medical research has not equitably included members of racial/ethnic minority groups or female and older individuals. There are limited data on participant demographic characteristics in vaccine trials despite the importance of these data to current trials aimed at preventing coronavirus disease 2019., Objective: To investigate whether racial/ethnic minority groups and female and older adults are underrepresented among participants in vaccine clinical trials., Design, Setting, and Participants: This cross-sectional study examined data from completed US-based vaccine trials registered on ClinicalTrials.gov from July 1, 2011, through June 30, 2020. The terms vaccine, vaccination, immunization, and inoculation were used to identify trials. Only those addressing vaccine immunogenicity or efficacy of preventative vaccines were included., Main Outcomes and Measures: The numbers and percentages of racial/ethnic minority, female, and older individuals compared with US census data from 2011 and 2018. Secondary outcome measures were inclusion by trial phase and year of completion., Results: A total of 230 US-based trials with 219 555 participants were included in the study. Most trials were randomized (180 [78.3%]), included viral vaccinations (159 [69.1%]), and represented all trial phases. Every trial reported age and sex; 134 (58.3%) reported race and 79 (34.3%) reported ethnicity. Overall, among adult study participants, White individuals were overrepresented (77.9%; 95% CI, 77.4%-78.4%), and Black or African American individuals (10.6%; 95% CI, 10.2%-11.0%) and American Indian or Alaska Native individuals (0.4%; 95% CI, 0.3%-0.5%) were underrepresented compared with US census data; enrollment of Asian individuals was similar (5.7%; 95% CI, 5.5%-6.0%). Enrollment of Hispanic or Latino individuals (11.6%; 95% CI, 11.1%-12.0%) was also low even among the limited number of adult trials reporting ethnicity. Adult trials were composed of more female participants (75 325 [56.0%]), but among those reporting age as a percentage, enrollment of participants who were aged 65 years or older was low (12.1%; 95% CI, 12.0%-12.3%). Black or African American participants (10.1%; 95% CI, 9.7%-10.6%) and Hispanic or Latino participants (22.5%; 95% CI, 21.6%-23.4%) were also underrepresented in pediatric trials. Among trials reporting race/ethnicity, 65 (48.5%) did not include American Indian or Alaska Native participants and 81 (60.4%) did not include Hawaiian or Pacific Islander participants., Conclusions and Relevance: This cross-sectional study found that among US-based vaccine clinical trials, members of racial/ethnic minority groups and older adults were underrepresented, whereas female adults were overrepresented. These findings suggest that diversity enrollment targets should be included for all vaccine trials targeting epidemiologically important infections.

Tubulointerstitial nephritis and renal tubular acidosis are well-known renal involvements with primary Sjögren's syndrome. However, several types of glomerulonephritis such as membranoproliferative glomerulonephritis and membranous nephropathy are also known to develop in patients with this syndrome. We here report a case of membranous nephropathy that developed 8 years after a diagnosis of primary Sjögren's syndrome in a female patient. Interestingly, the deposition was not identified by routine immunofluorescence using snap frozen tissue, but was revealed by immunofluorescence on formalin-fixed paraffin-embedded sections treated with proteinase K. We further performed immunofluorescence analysis on the treated paraffin-embedded sections with the identified antigen but found that the deposited IgG was not monoclonal and that serum amyloid P, a sensitive marker for membranous-like glomerulopathy with masked IgG κ deposits, was not evident in the glomeruli. To the best of our knowledge, this report depicted the first case of masked polyclonal IgG deposits and further analysis is needed to clarify the underlying mechanisms of IgG masking and possible association with autoantibodies.

Blood pressure (BP) is characterized by spontaneous oscillation over time, which is described as BP variability (BPV). The current study aimed to investigate whether short-term BPV was correlated with hypertensive nephropathy in Han Chinese individuals with hypertension. A single-center prospective cohort study of 300 Han Chinese participants with hypertension was conducted in Taiwan. Five different BPV parameters were derived from ambulatory BP monitoring (ABPM), including standard deviation (SD), weighted SD (wSD), coefficient of variation (CoV), successive variation (SV), and average real variability (ARV). Renal event was defined as > 50% reduction in baseline estimated glomerular filtration rate (eGFR). The average age of the participants was 63.5 years. The baseline eGFR was 84.5 mL/min/1.73 m 2 . The participants were divided into two groups according to the wSD of systolic BP (SBP). Survival was assessed via a Kaplan-Meier analysis. During the 4.2-year follow-up, the participants with the highest SBP wSD tertile had a greater number of renal events (6.0%) than their counterparts (0.5%) (log-rank test, p = .007). The Cox proportional hazard regression model was used to assess the independent effects of BPV, and results showed that 24-h SBP (HR = 1.105; 95% CI = 1.020-1.197, p = .015) and 24-h DBP (HR = 1.162; 95% CI = 1.004-1.344, p = .044) were independently associated with renal events. However, BPV parameters were only associated with renal events univariately, but not after adjusting for baseline characteristics, 24-h mean BP, and office BP. Therefore, the risk of hypertensive nephropathy was independently associated with 24-h mean BP, but not with ambulatory BPV, in Han Chinese participants with hypertension., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

In this study, we compared the metabolic properties of the Asian staples rice and noodles, which are typically high in glycaemic index (GI), to two types of spaghetti. It is hypothesised that pasta can be a healthy replacement, particularly amongst the Asian population. Thirty Chinese and Indian subjects (17 men, 13 women; BMI: 18.5-25 kg/m 2 ) participated in this randomised crossover trial. On seven occasions, they consumed a glucose reference drink (3 times), white rice, wheat-based mee pok noodles, semolina spaghetti and wholegrain spaghetti. Blood samples were taken to measure glucose and insulin response over a period of 3 h. The current evaluation showed that semolina spaghetti and wholegrain spaghetti can be classified as low GI products, with a GI of 53 and 54, respectively, significantly lower than wheat based mee pok noodles (74) and rice (80) ( p < 0.005). In addition, both spaghettis had a lower insulin response compared to rice ( p < 0.05). Furthermore, there was no difference in glucose or insulin response between semolina and wholegrain spaghetti. After controlling for gender, ethnicity, fat and fat free mass (kg), the glucose and insulin results did not change. In conclusion, wheat-based pasta can be helpful to modify the carbohydrate-rich Asian diet. Notably, there was no effect of gender, ethnicity and body composition on the glycaemic and insulinaemic response. We speculate that the starch-protein structure as a result of the spaghetti production process is a major driver of its favourable metabolic properties.

Purpose: We aimed to conduct psychometric tests for the Chinese version of ICECAP-A and compare the differences between ICECAP-A and EQ-5D-3L for patients with T2DM and explore the relationship between clinical conditions and ICECAP-A through diabetes-related clinical indicators., Methods: Data were collected from a sample of 492 Chinese T2DM patients. The reliability and validity of the ICECAP-A were verified. Exploratory factor analysis (EFA), correlation analysis and regression analysis were conducted for both the ICECAP-A and EQ-5D-3L., Results: Our results show that the Chinese version of ICECAP-A has good internal consistency with an overall Cronbach's Alpha coefficient of 0.721. The mean scores of ICECAP-A and EQ-5D-3L are 0.85 vs. 0.94. A weak correlation (r = 0.116) was found between the ICECAP-A tariff and EQ-5D-3L utility. EFA showed that although the five dimensions of the ICECAP-A and EQ-5D-3L scales were loaded into two different factors respectively. However, the two scales captured different dimensions of quality of life and can complement each other. The ICECAP-A, EQ-5D-3L, and EQ-VAS scores showed differences across different socio-demographic characteristics and clinic conditions groups., Conclusion: The Chinese version of the ICECAP-A capability instrument can be for assessing outcomes in adults with T2DM. It may capture more dimensions of QoL than traditional Health-related QoL (HRQoL) instruments and may be useful for economic evaluations of health care and social care for people with T2DM or other chronic diseases.

Purpose: To investigate the distribution of white-to-white (WTW) distance and its associations with other biometric parameters in Chinese cataractous eyes., Methods: Data on 39,986 eyes from 23,627 Chinese cataract patients were analyzed. Ocular biometric parameters, including WTW distance, corneal curvature, anterior chamber depth (ACD), lens thickness (LT), central corneal thickness (CCT), and axial length (AL), were obtained using the ZEISS IOLMaster 700., Results: The mean age of patients was 63.7 ± 12.4 years, and 57.61% were female. The mean WTW distance was 11.69 ± 0.46 mm. The WTW distance was larger in male patients than in female patients for all age groups (all P < 0.001). The WTW distance was positively correlated with corneal curvature and ACD and negatively correlated with age, LT, and CCT (all P < 0.001). Multivariable analysis revealed that a larger WTW distance was associated with younger age; male gender; larger corneal curvature, ACD, and LT; and thinner CCT (all P < 0.001). Notably, the association between WTW distance and AL was not linear. As the AL increased, the WTW distance initially increased, reached a peak in the group with ALs of 24.5 to 26 mm, and then slowly decreased. However, all of the myopic eyes (AL > 24.5 mm) still had larger WTWs than the normal and short eyes (AL ≤ 24.5 mm)., Conclusions: In Chinese cataractous eyes, the WTW distance was larger in younger male patients with flatter corneas, deeper anterior chambers, thicker lenses, and thinner central corneas. The association between WTW distance and AL was not linear, and WTW distance was the largest in eyes with ALs of 24.5 to 26 mm.

Purpose: To evaluate long-term rates of repeated keratoplasty after endothelial keratoplasty (EK), and to explore risk factors associated with graft failure., Design: Retrospective, cohort study., Methods: Population-based using 2010-2019 Medicare carrier claims., Study Population: Medicare beneficiaries aged ≥65 years who underwent endothelial keratoplasty (EK) procedures. Main outcome measures were 1) occurrence of repeated keratoplasty for the overall cohort as well as stratified by clinical indication, and 2), risk factors associated with repeated keratoplasty. The probability of undergoing repeated keratoplasty for different indications was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was constructed to determine patient and physician factors associated with the risk of repeated keratoplasty., Results: A total of 94,829 Medicare EK procedures (N = 71,040 unique patients) were included in the analysis. Over the study period, 11,013 of 94,829 EK procedures were followed by repeated keratoplasty. The overall probability of receiving a repeated keratoplasty was 6.1% at 6 months, 7.6% at 1 year, 14.3% at 5 years and 16.9% at 8 years. The probability of repeated keratoplasty was highest for procedures performed for prior failed grafts: 10.2% at 1 year, 29.9% at 8 years. Whereas 6.4% and 11.4% of grafts performed for Fuchs' endothelial dystrophy (FED) required repeated keratoplasty at 1 and 8 years of follow-up, respectively. For bullous keratoplasty and/or corneal edema, 8.6% and 22% of grafts underwent repeated keratoplasty at 1 and 8 years, respectively. In a multivariate analysis, patient factors associated with increased risk of repeated keratoplasty were black (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.20-1.38) or Asians (HR: 1.26; 95% CI: 1.10-1.45) having a glaucoma diagnosis (HR: 1.53; 95% CI: 1.46-1.60), prior glaucoma surgery (HR: 1.26; 95% CI: 1.18-1.35), and concurrent glaucoma surgery (HR: 1.31; 95% CI: 1.20-1.44). Surgeons with higher EK volumes had a decreased risk of repeated keratoplasty. Physicians who graduated medical school >30 years previously had increased risk of repeated keratoplasty compared to those who graduated within 10 years (HR: 1.16; 95% CI: 1.10-1.23)., Conclusions: Blacks or Asians, comorbid glaucoma, concurrent or prior glaucoma surgery, and lower volumes of surgery are associated with increased risk of repeated keratoplasty. Racial disparities identified in this study warrant further investigation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Peer volunteers have been found to be effective in delivering psychosocial interventions when they come from the same culture and share similar experiences as participants. We examined the clinical utility (feasibility and preliminary effectiveness) of a community-based, manualized, peer-delivered group counselling program to address the need for culturally responsive counselling for parents of children with autism in the South Asian community. Sixty-three parents (M age  = 43.7 years, 68% mothers) participated in the program, and reported high stable program satisfaction across sessions. Further, parents reported improved mental health and quality of life following involvement in the program, with changes noted even after the first session. Further research is warranted to assess the efficacy of this kind of parent support intervention.

Background: Ethnic phenotypic differences in Parkinson's disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials., Objective: To investigate (i) whether there are non-motor symptoms (NMS)- and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the differences between the groups., Methods: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment; additional measurements included disease and motor stage, comorbidity, sociodemographic parameters and brain MRI imaging., Results: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain "miscellaneous") and Asian (total score and domains "sleep/fatigue", "mood/apathy" and "perception/hallucinations") than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts., Conclusion: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities.

Purpose: To determine the changes in optical coherence tomography (OCT) color probability codes and diagnostic ability for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) analysis after applying Chinese and white subjects normative databases., Design: Cross-sectional study., Methods: This study enrolled 219 healthy eyes (108 white and 111 Chinese patients) to construct an ethnicity-specific normative database for pRNFL and macular GCC thickness, which was tested then in 180 eyes with or without glaucoma (102 white and 78 Chinese patients). The percent of change of color probability codes were evaluated after applying the original built-in and the ethnicity-specific normative databases, respectively. Sensitivity and specificity were calculated to evaluate the change in diagnostic ability to detect glaucoma., Results: Healthy white subjects had a thinner pRNFL than Chinese subjects in the overall average thickness as well as the superior, inferior, and temporal quadrants (P < .001). Macular GCC did not differ between ethnicities. After applying an ethnicity-specific normative database, the percent of pRNFL abnormal color code labels decreased significantly for the overall average thickness in the white subjects. This resulted in a significant increase in the specificity to detect glaucoma in the white population (P < .001). No significant changes were seen when applying an ethnicity-specific normative database for macular GCC thickness., Conclusions: After applying an ethnicity-specific normative database, the percent of pRNFL abnormal color codes decreased significantly, improving the specificity to detect glaucoma in the white population. These findings suggest there may be utility in having ethnicity-specific normative databases for pRNFL thickness., (Copyright © 2020 Elsevier Inc. All rights reserved.)