Identification of chikusetsusaponin IVa as a novel lysine-specific demethylase 1 inhibitor that ameliorates high fat diet-induced MASLD in mice.

Diet-induced metabolic dysfunction steatotic liver disease (MASLD) is also called as non-alcoholic fatty liver disease (NAFLD) with limited effective strategies available. We previously have shown that chikusetsusaponin IVa (CHS), a dietary saponin from herbs in South American known for their metabolic benefits, mitigates diet-induced diabetes. In this study we investigated the beneficial effects of CHS on MASLD and the underlying mechanisms.

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

Purpose: The purpose of this study was to describe genotype-phenotype associations and novel insights into genetic characteristics in a trio-based cohort of inherited eye diseases (IEDs).

Methods: To determine the etiological role of de novo mutations (DNMs) and genetic profile in IEDs, we retrospectively reviewed a large cohort of proband-parent trios of Chinese origin. The patients underwent a detailed examination and was clinically diagnosed by an ophthalmologist.

Genotypic spectrum and phenotype correlations of EYS-associated disease in a Chinese cohort.

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.

Frequency and phenotypic characteristics of RPE65 mutations in the Chinese population.

Background: The retinoid isomerohydrolase RPE65 has received considerable attention worldwide since a successful clinical gene therapy was approved in 2017 as the first treatment for vision loss associated with RPE65-mediated inherited retinal disease. Identifying patients with RPE65 mutations is a prerequisite to assessing the patients' eligibility to receive RPE65-targeted gene therapies, and it is necessary to identify individuals who are most likely to benefit from gene therapies. This study aimed to investigate the RPE65 mutations frequency in the Chinese population and to determine the genetic and clinical characteristics of these patients.

Evaluation of the Genetic Variation Spectrum Related to Corneal Dystrophy in a Large Cohort.

Aims: To characterize the genetic landscape and mutation spectrum of patients with corneal dystrophies (CDs) in a large Han ethnic Chinese Cohort with inherited eye diseases (IEDs).

Methods: Retrospective study. A large IED cohort was recruited in this study, including 69 clinically diagnosed CD patients, as well as other types of eye diseases patients and healthy family members as controls.

Novel variants of ABCA4 in Han Chinese families with Stargardt disease.

Background: Stargardt disease (STGD1) is a common recessive hereditary macular dystrophy in early adulthood or childhood, with an estimated prevalence of 1:8000 to 1:10,000. ABCA4 is the causative gene for STGD1. The current study aims at identifying the novel disease-related ABCA4 variants in Han Chinese families with STGD1 using next-generation sequencing (NGS).

Comprehensive analysis of genetic and clinical characteristics of 30 patients with X-linked juvenile retinoschisis in China.

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.

Mutation Screening of mtDNA Combined Targeted Exon Sequencing in a Cohort With Suspected Hereditary Optic Neuropathy.

Purpose: Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the two commonest forms of hereditary optic neuropathy. The aim of this study was to comprehensively investigate the incidence and spectrum of mutations in patients with suspected hereditary optic neuropathy by combining mitochondrial DNA (mtDNA) genome-wide and targeted exon sequencing.

Methods: A cohort of 1101 subjects were recruited to participate in the study, comprising 177 families (177 probands and their family members, a total of 537 subjects, including 254 patients) and 164 sporadic cases with suspected hereditary optic neuropathy, and 400 unrelated control subjects for genetic analysis: all subjects (including control subjects) underwent a comprehensive ophthalmologic examination and were subjected to sequencing analysis of mtDNA genome-wide and targeted exon.

Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses.

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.

Panel-based targeted exome sequencing reveals novel candidate susceptibility loci for age-related cataracts in Chinese Cohort.

Background: Age-related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis.

Genetic and clinical findings of panel-based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa.

Background: Panel-based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa.

Methods: A total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel-based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination.

Genetic and clinical analysis in Chinese patients with retinitis pigmentosa caused by EYS mutations.

Background: Panel-based targeted exome sequencing was applied to identify the pathogenic variants and genetic characteristics of retinitis pigmentosa (RP) in two Chinese families, and to gain a deeper understanding of the relationship between clinical manifestations and genotypes.

Methods: A total of 17 subjects, comprising two probands (total patients: four subjects) and their family member, were recruited in this study. All subjects underwent comprehensive ophthalmic examinations and clinical evaluations, and the complete history and medical records were collected according to the standard procedures.

Expanding the clinical and genetic spectrum of Heimler syndrome.

Background: Heimler syndrome (HS) is a rare hereditary systemic disorder, partial clinically overlapping with Usher syndrome. So far, our knowledge of HS is very limited, many cases are misdiagnosed or may not even be diagnosed at all. This study aimed to analyze the clinical and genetic characteristics of HS, and to evaluate potential phenotype-genotype correlations.

Next-generation sequencing-aided precise diagnosis of Stickler syndrome type I.

Purpose: To explore an early, rapid and precise diagnosis of Stickler syndrome type I (STL1) and to enrich the spectrum of COL2A1 mutations in the Chinese population, which is poorly studied at present.

Methods: In the current study, we analysed 115 patients with high myopia by next-generation sequencing and identified five STL1 patients from four unrelated Chinese families. The clinical features of all patients were reviewed in detail.

Gene Screening in a Chinese Cohort With Stargardt Disease: Identification of 37 Novel Variants.

To clarify the mutation spectrum and frequency of in a Chinese cohort with Stargardt disease (STGD1). A total of 153 subjects, comprising 25 families (25 probands and their family members) and 71 sporadic cases, were recruited for the analysis of variants. All probands with STGD1 underwent a comprehensive ophthalmologic examination.

Mutation spectrum of the bestrophin-1 gene in a large Chinese cohort with bestrophinopathy.

Background: Bestrophin-1 () gene is associated with a wide range of ocular phenotypes, collectively termed as bestrophinopathy. The aim of the current study was to identify the mutation spectrum of in a large cohort of Chinese patients with bestrophinopathy.

Methods: Patients clinically suspected of bestrophinopathy were screened using multigene panel testing.

Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa.

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.

A novel mutation in , causative of autosomal dominant retinitis pigmentosa, using the BGISEQ-500 sequencer.

Aim: To study the genes responsible for retinitis pigmentosa.

Methods: A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer's instructions.

Targeted next-generation sequencing analysis identifies novel mutations in families with severe familial exudative vitreoretinopathy.

Purpose: Familial exudative vitreoretinopathy (FEVR) is a genetically and clinically heterogeneous disease, characterized by failure of vascular development of the peripheral retina. The symptoms of FEVR vary widely among patients in the same family, and even between the two eyes of a given patient. This study was designed to identify the genetic defect in a patient cohort of ten Chinese families with a definitive diagnosis of FEVR.

Mechanistic prediction of food effects for Compound A tablet using PBPK model.

Physiologically based pharmacokinetic (PBPK) modeling has been extensively used to study the factors of effect drug absorption, distribution, metabolize and extraction progress in human. In this study, Compound A(CPD A) is a BCS Class II drug, which has been extensive applied in clinical as lipid-lowering drug, administered orally after food, they displayed positive food effects in human, A PBPK model was built to mechanistic investigate the food effect of CPD A tablet in our study. By using gastroplus™ software, the PBPK models accurately predicted the results of food effects and predicted data were within 2-fold error of the observed results.

Simultaneous determination of subutinib and its active metabolite in human plasma by LC-MS/MS: Application to pharmacokinetic study.

A selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and its active metabolite in human plasma. Plasma samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C18 (150mm×2.1mm, 3.

Development of a LC-MS/MS method for the estimation of clinofibrate in human urine.

A highly sensitive and rapid liquid chromatography-tandem mass spectrometry method was developed for the determination of clinofibrate in human urine. The analyte and IS were extracted through a simple protein precipitation by the mixture of acetonitrile and 1 mol/L hydrochloric acid (95:5, v/v) and separated on an Inspire C18 (150 mm x 4.6 mm I.