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Introduction: Hereditary ataxias demonstrate a high degree of clinical and genetic heterogeneity. Understanding the genetic etiology of hereditary ataxias is crucial for genetic counseling and clinical management.Methods: The clinical and genetic data of patients with familial or sporadic ataxias who referred to our tertiary medical center were retrospectively analyzed. Probands in this study underwent SCA repeat expansion panel firstly to screen for repeat expansion SCAs; those with negative results had NGS-targeted panels or WES testing to detect conventional mutations.Results: A total of 223 patients were enrolled from 206 families. 5 kinds of coexisting SCA repeat expansions were observed (SCA3/SCA17, SCA3/SCA8, SCA2/SCA8, SCA3/SCA12 and SCA8/SCA12) in 12 patients from 8 families, among which SCA2/SCA8, SCA8/SCA12 and SCA3/SCA12 were reported for the first time. The coexistence of expanded SCA3 with SCA17 alleles was the most common in our study. NGS identified pathogenic/likely pathogenic variants in 12 ataxia causative genes in 13 probands. Spastic paraplegia ataxia was the most common diagnosis. Six novel mutations were detected in five ataxia-related genes.Conclusion: Coexistence may not specific to a certain SCA subtype and the frequency might have been underestimated before. SCA repeat expansion panel should be considered in patients with overlapping SCA features. In addition, our study broadened the conventional mutation spectrum in ataxia-related genes. These results facilitate a better understanding of the genetic basis for hereditary ataxias. [ABSTRACT FROM AUTHOR]

The adverse effects of short-term exposure to PM 2.5 and its components on hospital admissions for threatened and spontaneous abortions (TSAB) are still controversial. Data on daily hospitalizations for TSAB and PM 2.5 and its components, including sulfate (SO 4 2−), nitrate (NO 3 −), ammonium salt (NH 4 +), organic matter (OM), and black carbon (BC), were collected from January 2015 to December 2021 (total 2,557 days) in five cities in China. Case-crossover analyses were conducted to investigate the short-term associations between PM 2.5 and its components and TSAB. Additionally, the modification effects by age (<35 and ≥35 years), season (cold and warm seasons), and the "Three-Year Action Plan to Win the Blue Sky Defense War" (before and after implementation) on the above associations were further conducted. For each 10 μg/m3 (1 μg/m3 for BC) increase, the strongest relative risks (95% confidence intervals) of hospitalization for TSAB were 1.011 (1.001–1.021) for PM 2.5 in lag02, 1.060 (1.003–1.120) for SO 4 2− in lag02, 1.035 (1.000–1.070) for NO 3 − in lag02, 1.065 (1.009–1.124) for NH 4 + in lag02, 1.047 (1.008–1.088) for OM in lag01 and 1.029 (1.005–1.054) for BC in lag02 (all P <0.05). Furthermore, significant modifying effects of age and the Action Plan were found. The effects of NO 3 − (lag2), NH 4 + (lag2), and BC (lag2) were more pronounced in mothers aged ≥35 years and the effects of PM 2.5 (lag4), NO 3 − (lag4), NH 4 + (lag4), OM (lag4), and BC (lag4) was more pronounced in the period before the Action Plan was implemented (all P modification <0.05). Short-term exposure to ambient PM 2.5 and its components (SO 4 2−, NO 3 −, NH 4 +, OM, and BC) was related to increased risks of hospitalization for TSAB. The effects were more pronounced in mothers aged ≥35 years and the period before the Action Plan. [Display omitted] • Short-term PM 2.5 and its components exposure was positive with TSAB. • The deleterious effect was stronger in mothers aged ≥35 years. • The deleterious effect was stronger in the period before the Action Plan. [ABSTRACT FROM AUTHOR]

In this study, residues of 369 pesticides were determined in 123 banana samples by UPLC-Q-TOF/MS/MS to evaluate the potential risk of pesticide residues in bananas and investigate the quality and safety situation in Hainan province, China. The results indicated that 107 samples contained 1–10 residues. Insecticides and fungicides were the groups with the highest detection frequencies in bananas. The most frequently detected pesticides in bananas were pyraclostrobin (50.41%), prochloraz (38.21%), imidacloprid (33.33%), acetamiprid (25.20%) and carbendazim (19.51%); 13 samples were unqualified with the failure rate 10.57%. The index of food safety (IFS) of all detected pesticides in bananas was less than 1, and the value of the acute reference dose (ARfD) and acceptable daily intake (ADI) of pesticide residues detected in different populations were less than 100%, indicating an acceptable safety risk of the pesticide residues. As for risk coefficient (R), there was a high early warning risk for fluxapyroxad and imidacloprid, as well as a moderate early warning risk for propiconazole. According to the risk ranking, we found 3 kinds of medium-risk pesticides, including acetamiprid, difenoconazole and prochloraz. They should be considered in the key control risk factors and continuously monitored to protect people's health. However, undue concern was unnecessary since the assessment was based on a conservative assumption. • A fast, efficient and convenient general sample pretreatment method was established. • UPLC-LC/MS/MS non-targeted, high-throughput screening techniques were used. • The law of pesticide residues in bananas sold in Hainan Province was found out. • Early warning and exposure risk assessment of pesticides detected in bananas. • Acute and chronic risks were also assessed for dietary risk. [ABSTRACT FROM AUTHOR]

Background: Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by developmental delay, intellectual disability, microcephaly, coarse face and hypoplastic nail of the fifth digits. Heterozygous variants of different BAF complex-related genes were reported to cause CSS, including ARID1A and SMARCA4. So far, no CSS patients with ARID1A and SMARCA4 variants have been reported in China., Objective: The aim of the current study was to identify the causes of two Chinese patients with congenital growth deficiency and intellectual disability., Methods: Genomic DNA was extracted from the peripheral venous blood of patients and their family members. Genetic analysis included whole-exome and Sanger sequencing. Pathogenicity assessments of variants were performed according to the guideline of the American College of Medical Genetics and Genomics. The phenotypic characteristics of all CSS subtypes were summarized through literature review., Results: We identified two Chinese CSS patients carrying novel variants of ARID1A and SMARCA4 respectively. The cases presented most core symptoms of CSS except for the digits involvement. Additionally, we performed a review of the phenotypic characteristics in CSS, highlighting phenotypic varieties and related potential causes., Conclusions: We reported the first Chinese CSS2 and CSS4 patients with novel variants of ARID1A and SMARCA4. Our study expanded the genetic and phenotypic spectrum of CSS, providing a comprehensive overview of genotype-phenotype correlations of CSS., (© 2022. The Author(s) under exclusive licence to The Genetics Society of Korea.)

The phylogeny and speciation of subterranean zokors in China are unclear, as previous studies on morphology and limited molecular markers have generated conflicting results. This study unraveled the complex evolutionary history of eight zokor species in China based on de novo assembly at chromosome level and whole-genome sequencing of 23 populations. We found extensive phylogenetic discordances between nuclear and mitochondrial phylogenies, and different coalescent phylogenies, which could be explained by introgression and incomplete lineage sorting (ILS). The recent Qinghai-Tibet Plateau uplift (∼3.60 million y ago; Mya) drove Eospalax to speciate into clade A and clade B (∼3.22 Mya), and discordant phylogenies in this node were mainly attributed to introgression rather than ILS. Clade A rapidly diverged into three lineages due to geographical isolation and glaciation, while glaciation and C4 plant expansion contributed to the speciation of clade B. ILS contributed to the discordances of two rapidly radiated nodes rather than introgression. The effective population sizes (Ne’s) of all the species of Eospalax were affected by three glaciations. Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of all the species pairs. Positively selected genes putatively related to specific inhabitation adaptations were identified, such as heart development, neurogenesis, DNA repair, and immune response. Climate, geological tectonism, and C4 vegetation shaped the adaptation and speciation of zokors in China.

Essential oils from Chinese medicine are popular in the fields such as medicine, food, and cosmetics because of their unique biological characteristics. However, since essential oils are lipophilic compounds with high volatility, poor stability, and strong irritation, various preparation technologies need to be employed to improve stability, reduce irritation, and increase bioavailability. At present, a variety of preparation technologies have been applied to the encapsulation of essential oils. Various encapsulation strategies are formed because of different delivery systems featured with multiple principles and characteristics and are widely used to improve the stability of essential oils. Essential oils of Chinese medicine are widely used in the medical field, and they are under continuous innovation and development in clinical research, the pharmaceutical industry, medical products, etc. The present study summarized various delivery systems that could improve the stability of essential oils and reviewed the applications of essential oils encapsulated in the delivery systems in the medical field to provide re-ferences for the improvement of stability of essential oils and their safety, efficiency, and wide use in the medical field.

Objectives: The aim of this study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China., Methods: We compared the efficiency and performance of 6 parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic, and logistic) based on cytosine-adenine-guanine (CAG) repeat length at ATXN3 to predict the probability of AAO in the largest cohort of patients with SCA3/MJD. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike information criterion (AIC), bayesian information criterion (BIC), Nagelkerke R-squared (Nagelkerke R^2), and Cox-Snell residual plot, were used to identify the best model., Results: Among these 6 parametric survival models, the logistic model had the lowest -2 log-likelihood (6,560.12), AIC (6,566.12), and BIC (6,566.14) and the highest value of Nagelkerke R^2 (0.54), with the closest graph to the bisector Cox-Snell residual graph. Therefore, the logistic survival model was the best fit to the studied data. Using the optimal logistic survival model, we indicated the age-specific probability distribution of AAO according to the CAG repeat size and current age., Conclusions: We first demonstrated that the logistic survival model provided the best fit for AAO prediction in patients with SCA3/MJD from mainland China. This optimal model can be valuable in clinical and research. However, the rigorous clinical testing and practice of other independent cohorts are needed for its clinical application. A unified model across multiethnic cohorts is worth further exploration by identifying regional differences and significant modifiers in AAO determination., (© 2021 American Academy of Neurology.)

Background: In polyglutamine (polyQ) disease, the investigation of the prediction of a patient's age at onset (AAO) facilitates the development of disease-modifying intervention and underpins the delay of disease onset and progression. Few polyQ disease studies have evaluated AAO predicted by machine-learning algorithms and linear regression methods., Objective: The objective of this study was to develop a machine-learning model for AAO prediction in the largest spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) population from mainland China., Methods: In this observational study, we introduced an innovative approach by systematically comparing the performance of 7 machine-learning algorithms with linear regression to explore AAO prediction in SCA3/MJD using CAG expansions of 10 polyQ-related genes, sex, and parental origin., Results: Similar prediction performance of testing set and training set in each models were identified and few overfitting of training data was observed. Overall, the machine-learning-based XGBoost model exhibited the most favorable performance in AAO prediction over the traditional linear regression method and other 6 machine-learning algorithms for the training set and testing set. The optimal XGBoost model achieved mean absolute error, root mean square error, and median absolute error of 5.56, 7.13, 4.15 years, respectively, in testing set 1, with mean absolute error (4.78 years), root mean square error (6.31 years), and median absolute error (3.59 years) in testing set 2., Conclusion: Machine-learning algorithms can be used to predict AAO in patients with SCA3/MJD. The optimal XGBoost algorithm can provide a good reference for the establishment and optimization of prediction models for SCA3/MJD or other polyQ diseases. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Background: Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China. HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum -induced liver injury (PM-DILI). However, little is known about the relationship between single-nucleotide polymorphisms (SNPs) and PM-DILI., Aim: To identify SNPs that indicate susceptibility to PM-DILI., Methods: We conducted a systematic study enrolling 382 participants from four independent hospitals, including 73 PM-DILI patients, 118 patients with other drug-induced liver injury (other-DILI) and 191 healthy controls. Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects. Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients, 118 other-DILI patients and 183 healthy controls using the MassARRAY system. HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients. The Han-MHC database was selected as a population control for HLA-B analysis. P < 6.25 × 10 -3 after Bonferroni correction was considered significant., Results: The frequencies of rs111686806 in the HLA-A gene, rs1055348 in the HLA-B gene, and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%, P = 1.72 × 10 -5 , odds ratio (OR) = 3.96, 95% confidence interval (CI): 2.21-7.14; 42.5% vs 8.6%, P = 1.72 × 10 -19 , OR = 13.62, 95%CI: 7.16-25.9; 22.9% vs 8.1%, P = 4.64 × 10 -6 , OR = 4.1, 95%CI: 2.25-7.47]. Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group (42.5% vs 13.6%, P = 1.84 × 10 -10 , OR = 10.06, 95%CI: 5.06-20.0), which suggested that it is a specific risk factor for PM-DILI. rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group. Furthermore, HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9% ( P = 4.30 × 10 -11 , OR = 11.11, 95%CI: 5.57-22.19) in the other-DILI group and 2.7% ( P = 6.22 × 10 -166 , OR = 62.62, 95%CI: 35.91-109.20) in the Han-MHC database., Conclusion: rs111686806, rs1055348, and rs202047044 are associated with PM-DILI, of which, rs1055348 is specific to PM-DILI. As a tag for HLA-B*35:01 , rs1055348 may become an alternative predictive biomarker of PM-DILI., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The effect of blood pump flow rate on the cardiac functions of hemodialysis patients with arteriovenous fistula (AVF) is largely unknown. This study aimed to investigate if blood pump flow rate (Qb) and AVF access flow rate (Qa) can affect the cardiac function of Chinese hemodialysis patients. A total of 72 patients undergoing AVF hemodialysis were included from March 2010 to June 2014 and dichotomized into the high- and low-flow groups using the medians of Qb (220 mL/min) and Qa (1000 mL/min) as the cutoffs. The cardiac function parameters were measured by ultrasound dilution technique within the first (t + 30) and the last (t - 30) 30 min of dialysis. At t + 30, Qb-high group had significantly higher systolic blood pressure (SBP) and mean arterial pressure (MAP) than Qb-low group. At t - 30, Qb-high group had higher SBP, diastolic blood pressure (DBP), and MAP than Qb-low group. Qa-high group had higher SBP, MAP, cardiac output (CO), cardiac index (CI), central blood volume (CBV), and lower peripheral resistance than Qa-low group. Multiple linear regression showed that at t - 30, Qb was positively correlated with SBP and MAP. Qa was positively correlated with CO, CI, CBV, and PR but negatively correlated with heart rate. Although Qb > 220 mL/min and Qa >1000 mL/min would elevate some parameters, the means of SBP, DBP, MAP remain within the normal range, indicating that appropriate increase in blood pump flow rate has little effect on the cardiac function of hemodialysis patients., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)