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Background: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. Methods: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. Results: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. Conclusions: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2. [ABSTRACT FROM AUTHOR]

To compare the effects of short-term exposure to particulate matter (PM) with different particle sizes on first-ever stroke risk in the middle-aged and elderly Chinese population. Health information was collected from the China National Stroke Screening Survey (CNSSS) from March 1, 2013, to April 10, 2015. Ambient exposures to PM 1 , PM 2.5 , and PM 10 were obtained from ChinaHighAirPollutants (CHAP) Grid data. Case-crossover design was used to estimate the increase of first-ever stroke risk per 10 μg/m3 increase in ambient exposures to different size particles. We used distributed lag linear model (DLM) to estimate the hysteresis effects of particle exposures. In addition, in order to assess the effect modification of long-term exposure, we did a stratified analysis using median exposure as the dividing line. We included 1326 first-ever stroke events from 242 communities in the present study. We found that effects on first-ever stroke risk increased with the decrease in particle size. The percent increases of first-ever stroke risk increased by 6.6% (95% CI: 1.4, 12.0), 3.3% (95% CI: 0.5, 6.1), and 0.6% (95% CI: -1.2, 2.6) per 10 g/m3 increases in PM 1 , PM 2.5 , and PM 10 exposures in lag 0–2 days, respectively. Furthermore, the cumulative effect of PM on first-ever stroke reached its peak at distinct time points under different layers of long-term PM exposure. In areas with low PM exposure, the cumulative effects of the three kinds of particles on stroke reached their peak in lag1 day, while the cumulative effect peaked in lag3 day in areas with high PM exposure. This study found that smaller particles had a stronger short-term effect on first-ever stroke. We also found that people in areas with long-term exposures to lower levels were more sensitive to short-term exposures. These results have public health significance for stroke prevention and air pollution reduction. [Display omitted] • The effects of PM on first-ever stroke in a large area were evaluated. • The impacts of PM increase with decreasing particle size. • The short-term effects of PM were larger in areas with lower long-term exposure levels. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term efficacy and quality of life concerning sacrospinous ligament fixation (SSLF) using conventional instruments for Chinese women with symptomatic stage 2 and 3 apical prolapse. Methods: This single‐arm prospective cohort study was conducted at our hospital between October 2011 and December 2018. Eligible participants were followed up over 3 years after surgery. The primary surgical outcome was composite surgical failure. Secondary outcomes included rate of satisfaction, quality of life (QoL) scores, and long‐term complications. Results: Fifty‐nine patients were enrolled (mean age 57.1 years), of whom 55 (93.22%) completed the 3‐year follow up. At year 3, the composite failure rate was 21.34% (95% confidence interval [CI] 9.30%–31.79%), and satisfaction rate was 81.40% (95% CI 66.09%–91.08%). Right thigh pain and de novo dyspareunia occurred in 1.8% and 14.6% patients after year 1, respectively, but at year 3 there were no complications. Lower urinary tract symptoms were present in 5.5% of patients. Improvement was found in urinary symptoms and prolapse symptoms, but sexual function showed no significant change. Conclusions: Compared with results at year 1, complication rates of SSLF decreased at year 3. The composite failure rate was relatively low and satisfaction rate was relatively high at year 3. Prolapse and urinary symptoms improved significantly after surgery. Synopsis: Sacrospinous ligament fixation using conventional instruments is feasible and promising for Asian women in low‐income countries for symptomatic stage 2 and 3 apical prolapse. [ABSTRACT FROM AUTHOR]

The population history of Southeast (SE) China remains poorly understood due to the sparse sampling of present‐day populations and limited modeling with ancient genomic data. We report genome‐wide genotyping data from 207 present‐day Han Chinese and Hmong‐Mien (HM)‐speaking She people from Fujian and Taiwan Island, SE China. We coanalyzed 66 Early Neolithic to Iron Age ancient Fujian and Taiwan Island individuals obtained from previously published works to explore the genetic continuity and admixture based on patterns of genetic variations of the high‐resolution time transect. We found the genetic differentiation between northern and southern East Asians was defined by a north–south East Asian genetic cline and our studied southern East Asians were clustered in the southern end of this cline. The southeastern coastal modern East Asians are genetically similar to other southern indigenous groups as well as geographically close to Neolithic‐to‐Iron Age populations, but they also shared excess alleles with post‐Neolithic Yellow River ancients, which suggested a southward gene flow on the modern southern coastal gene pool. In addition, we identified one new HM genetic cline in East Asia with the coastal Fujian HM‐speaking She localizing at the intersection between HM and Han clines. She people show stronger genetic affinity with southern East Asian indigenous populations, with the main ancestry deriving from groups related to southeastern ancient indigenous rice farmers. The southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to rice farmers, which was consistent with the northern China origin of modern southeastern Han Chinese and in line with the historically and archaeologically attested southward migrations of Han people and their ancestors. Our estimated north–south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze Age to historic periods, suggesting the recent large‐scale population migrations and subsequent admixture participated in the formation of modern Han in SE Asia. [ABSTRACT FROM AUTHOR]

The Han Chinese are the world's largest ethnic group residing across China. Shaanxi province in northern China was a pastoral–agricultural interlacing region sensitive to climate change since Neolithic times, which makes it a vital place for studying population dynamics. However, genetic studies of Shaanxi Han are underrepresented due to the lack of high‐density sampling and genome‐wide data. Here, we genotyped 700 000 single nucleotide polymorphisms (SNPs) in 200 Han individuals from nine populations in Shaanxi and compared with available modern and ancient Eurasian individuals. We revealed a north–south genetic cline in Han Chinese with Shaanxi Han locating at the northern side of the cline. We detected the western Eurasian‐related admixture in Shaanxi populations, especially in Guanzhong and Shanbei Han Chinese in proportions of 2%–4.6%. Shaanxi Han were suggested to derive a large part of ancestry (39%–69%) from a lineage that also contributed largely to ancient and present‐day Tibetans (85%) as well as southern Han, supporting the common northern China origin of modern Sino‐Tibetan‐speaking populations and southwestward expansion of millet farmers from the middle‐upper Yellow River Basin to the Tibetan Plateau and to southern China. The rest of the ancestry of Shaanxi Han was from a lineage closely related to ancient and present‐day Austronesian and Tai‐Kadai speaking populations in southern China and Southeast Asia. We also observed a genetic substructure in Shaanxi Han in terms of north–south‐related ancestry corresponding well to the latitudes. Maternal mitochondrial DNA and paternal Y‐chromosome lineages further demonstrated the aforementioned admixture pattern of Han Chinese in Shaanxi province. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling. We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed. Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy. The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses. Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy. [ABSTRACT FROM AUTHOR]

Ambient ozone (O 3) pollution has been associated with an increased risk of cardiovascular diseases. However, few studies have addressed the effect of O 3 exposure on electrocardiogram (ECG) abnormalities, a subclinical indicator of early damage to the cardiovascular system. This study aimed to examine the association between short-term exposure to O 3 and ECG abnormalities. We included 102,027 visits of 47,290 participants over 40 years old who had a normal ECG at baseline and then visited again at least once from the China National Stroke Screening Survey (CNSSS). Short-term ozone exposure concentrations were measured as averages of maximum daily 8-h O 3 concentrations over the two weeks prior to ECG measurements. The generalized estimation equations models were used to evaluate the association between O 3 exposure and ECG abnormalities. For every 10 µg/m3 increment in short-term O 3 concentration, the odds ratio of any ECG abnormality was 1.055 (95% confidence interval [CI] 1.045–1.064). For ECG-diagnosed cardiac arrhythmia, the odds ratio was 1.062 (95% CI 1.052–1.072). A nonlinear analysis showed a sublinear relationship between O 3 exposure and risk for ECG abnormalities. The association between O 3 exposure and ECG abnormalities varied by subpopulation. Our study provided new epidemiological evidence on the association between short-term O 3 exposure and ECG abnormalities. There is an urgent need to control ambient O 3 pollution to prevent cardiovascular events. [Display omitted] • Electrocardiogram abnormality as a subclinical indicator can reflect the early injury of cardiovascular system. • Short-term exposure to ozone is positively associated with ECG abnormalities in a large Chinese population. • Cardiovascular diseases should be prevented by reducing the occurrence of ECG abnormalities. [ABSTRACT FROM AUTHOR]