2-bromoacetamide exposure impairs oocyte maturation in mice and humans primarily via disrupting the cytoskeleton.

2-bromoacetamide (BAcAm) is an emerging class of unregulated disinfection by-products (DBPs), with potent cytogenetic and developmental toxicity in animals. However, whether BAcAm exerts toxic effects on mammalian oocyte quality remains to be elucidate. In this research, we investigated the effect of BAcAm on mouse and human oocyte maturation with an in vitro culture system. Our results revealed that BAcAm exposure hindered the extrusion of the first polar body, disrupted the spindle organization and reduced the competence of embryo development after fertilization in the mouse oocytes. Results of single-cell RNA sequencing (scRNA-seq) showed that 605 differentially expressed genes (DEGs) were identified in the BAcAm exposed mouse oocytes, among which 366 were up-regulated and 239 were down-regulated. Gene Ontology (GO) analysis further revealed that DEGs were mainly enriched in mitochondrial functions, oxidative stress, cytoskeleton, endoplasmic reticulum (ER), Golgi and protein synthesis, DNA damage and apoptosis. We then conducted further tests in these aspects and discovered that BAcAm exposure principally perturbed the function of microtubule and actin cytoskeleton. This finding was confirmed in human oocytes. Overall, our data suggest that BAcAm exposure disturbs the cytoskeleton function, thus impairing oocyte maturation. These data, for the first time, provide a comprehensive view for the toxic effects of BAcAm on oocyte maturation.

Effects of nutritional interventions on cognitive function in adult cancer survivors: A systematic review.

AIM: To evaluate the effectiveness and safety of nutritional interventions (i.e. nutritional support, dietary patterns and dietary supplements) on cognitive function in cancer survivors. DESIGN: Systematic review. METHODS: A systematic and comprehensive search of PubMed, Web of Science, the Cochrane Library, Embase, and CINAHL was conducted from the inception until March 10, 2023. The last search was conducted on December 10, 2023. REPORTING METHOD: PRISMA. RESULTS: A total of 59 randomized controlled trials were included for analysis. Nutritional support, dietary patterns and dietary supplements improved cognitive function in cancer survivors with no apparent safety concerns. The anti-inflammatory diet, the fasting-mimicking diet and the web-based diet significantly improved cognitive function. Whereas the ketogenic diet or dietary advice to consume more soluble dietary fibres and less insoluble dietary fibres and lactose could not. There was evidence from dietary supplements to support the beneficial effects of polyunsaturated fatty acid supplements, traditional herbal medicines and other supplements. CONCLUSIONS: Nutritional interventions have great promise for improving cognitive function in adult cancer survivors. Further validation of the nutritional interventions supported in this study in other survivors and exploration of more effective nutritional interventions are needed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This work can support the construction of nutritional support interventions and dietary guidance programs to prevent cancer-related cognitive decline. IMPACT: This work filled a gap in preventive strategies for cancer-related cognitive decline from a nutritional perspective. Nutritional support, dietary patterns, and dietary supplements can prevent cancer-related cognitive decline without serious safety concerns. This work highlighted nutritional interventions that have the potential to improve cognitive function in cancer survivors, benefiting the further construction of evidence-based nutritional intervention programs. PROTOCOL REGISTRATION: PROSPERO. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Post-ovulatory aging affects mitochondria, spindle and protein metabolism in mouse oocytes.

In brief: Post-ovulatory aging (POA) results in a decline in oocyte quality and embryonic developmental capacity although the underlying mechanisms remain elusive. This study provides comprehensive mRNA expression profiles of fresh and aging oocytes in mice for the first time. Abstract: POA impairs the quality of mammalian oocytes with harmful effects on the developmental potential of the embryo. This is a major problem for humans since it is associated with low rate of natural fertility, with high rate of spontaneous abortion and low efficiency of in vitro fertilization. However, the molecular mechanisms underlying this process remain unclear and new methods are demanded to control POA. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis on fresh and aging MII mouse oocytes and compared their global RNA transcription patterns. Nine hundred and twenty-one differentially expressed genes (DEGs) were identified. Five hundred and sixty-nine genes were downregulated, while 356 were upregulated in the group of aging oocytes. Gene ontology (GO) enrichment analysis demonstrated that a series of DEGs were significantly enriched involving mitochondrial functions, spindle functions and protein metabolism. The results of qPCR and a series of functional tests further confirmed that the disorder of mitochondrial functions, spindle functions and impairment of protein metabolism were actually involved in the progression of POA. In this study, panoramic mRNA expression profiles of fresh and aging oocytes were depicted and fully validated. Our data will provide a useful resource for further research on the regulation of gene expression of POA and suggest potential strategies to delay and reverse POA.

Developmental toxicity of 2-bromoacetamide on peri- and early post-implantation mouse embryos in vitro.

2-bromoacetamide (BAcAm), a new class of disinfection by-products (DBPs), is widely detected in drinking water across the world. Reports of the high cytogenetic toxicity of BAcAm have aroused public attention concerning its toxic effects on early embryonic development. In this study, we optimized an in vitro culture (IVC) system for peri- and early post-implantation mouse embryos and used this system to determine the developmental toxicity of BAcAm. We found that exposure to BAcAm caused a reduction in egg cylinder formation rate and abnormal lineage differentiation in a dose-dependent manner. Transcriptomic analysis further revealed that BAcAm exposure at early developmental stages altered the abundance of transcripts related to a variety of biological processes including gene expression, metabolism, cell proliferation, cell death and embryonic development, thus indicating its toxic effects on embryonic development. Thus, we developed a robust tool for studying the toxicology of chemicals at the early stages of embryonic development and demonstrated the developmental toxicity of BAcAm in the early embryonic development of mammals.

Factors influencing adherence to healthy eating behaviors among adult colorectal cancer survivors: a systematic mixed method review.

PURPOSE: Under the umbrella of social cognitive theory, we examined the influences of personal, environmental, and behavioral factors on adherence to healthy eating behaviors among colorectal cancer survivors. METHODS: Based on Pluye and Hong's framework, a systematic mixed studies review was conducted. An extensive search strategy was applied in PubMed, Web of Science, Embase, CINAHL, and PsycINFO (from date of record to 2022 January 22). The pillar integration process was employed to integrate the extracted data. The Mixed Methods Appraisal Tool was used to appraise the quality of all retained studies. RESULTS: Twenty-eight studies with a total sample size of 5106 were included in the analysis, with 15 quantitative studies, 12 qualitative studies, and 1 mixed method study. The critical appraisal showed that 22 of the 28 studies (79%) were rated with five stars, while 6 (21%) were rated with four stars. The personal factors influencing adherence to healthy eating behaviors among colorectal cancer survivors included outcome expectancies, self-efficacy, psychological factors, knowledge about healthy eating, demographic and disease characteristics, environmental factors incorporated outside information on healthy eating, power of surrounding people, social activities, cultural milieus, socioeconomic status, and education. The behavioral factors included self-regulation of diet, goals, and other behaviors closely related to healthy eating behaviors. CONCLUSIONS: Adherence to healthy eating behaviors among colorectal cancer survivors was influenced collectively by personal factors, environmental factors and behavioral factors.

Six kanshone C-derived sesquiterpenoid hybrids nardochalaristolones A-D, nardoflavaristolone A and dinardokanshone F from Nardostachys jatamansi DC.

Four sesquiterpenoid-chalcone hybrids (nardochalaristolones A-D, 1-4), a pair of epimeric sesquiterpenoid-flavonone hybrids ((2'S)- and (2'R)-nardoflavaristolone A, 5 and 6), and a sesquiterpenoid dimer (dinardokanshone F, 7), all sharing a kanshone C-derived sesquiterpenoid unit, were isolated from the underground parts of Nardostachys jatamansi (D.Don) DC. Their structures were elucidated by analysis of the extensive spectroscopic data, and the absolute configurations were established by analysis of 2D NMR spectroscopic data including NOESY data, combined with comparisons of experimental and calculated electronic circular dichroism spectra. Further, the plausible biosynthetic pathways for these compounds were proposed. And the results of SERT activity assay revealed that nardochalaristolones C-D (3 and 4) and nardoflavaristolone A (5 and 6) significantly enhanced SERT activity, while other compounds didn't show any SERT regulatory activities.

Genetic screening of SCNN1B and SCNN1G genes in early-onset hypertensive patients helps to identify Liddle syndrome.

BACKGROUND: Liddle syndrome is an autosomal dominant form of monogenic hypertension. Phenotypic variability makes it difficult to identify patients with Liddle syndrome, resulting in misdiagnosis and severe complications at early age. OBJECTIVES: To identify mutation in SCNN1B and SCNN1G genes in an adolescent with suspicious Liddle syndrome and his family members and to explore the screening target subjects of Liddle syndrome. METHODS: Genetic analysis of the C-terminus of SCNN1B and SCNN1G genes was conducted in an adolescent, with treatment-resistant hypertension and hypokalemia, who was suspected of having Liddle syndrome, and his family members. A Medline research of the reported cases with Liddle syndrome was also performed. RESULTS: A recurrent SCNN1B mutation, c.1853C>A (p.P618H), was detected in the 19-year-old male patient, and family screening identified five additional members who were heterozygous for the mutation. The diagnosis of Liddle syndrome was made in all affected individuals. Despite the phenotypic variability, a systematic review of 54 reported index cases revealed the early-onset hypertension, aged no more than 30 years, as a common feature. CONCLUSIONS: Genetic screening for Liddle syndrome should be considered in hypertensive subjects with early penetrance, maybe no more than 30 years, after exclusion of common secondary causes of hypertension.

Left Ventricular Non-Compaction: A Cardiomyopathy With Acceptable Prognosis in Children.

BACKGROUND: Data on children with left ventricular non-compaction (LVNC) is sparse. The purpose of this study was to evaluate its clinical profiles in a population of Chinese children. METHODS: From January 2010 to March 2016, consecutive Chinese children (aged <18 years) with LVNC diagnosed by cardiovascular magnetic resonance (CMR) were prospectively recruited at Fuwai Hospital. RESULTS: A total of 41 Chinese children (male: 28%; mean age: 14±4years) were included in this study. Left ventricular non-compaction was not detected in 13 (32%) patients at initial echocardiographic evaluation. Congenital heart disease (CHD) was found in 11 (27%) patients. Four (10%) patients had Wolff-Parkinson-White (WPW) syndrome. Mean left ventricular ejection fraction (LVEF) was 41±15%. Late gadolinium enhancement (LGE) was detected in eight (20%) subjects. During a mean follow-up of 2.9 years, four (9%) patients died or received heart transplantation. These patients had lower systolic blood pressure (91±10 vs. 108±14mmHg; p=0.02), diastolic blood pressure (57±7 vs. 68±8mmHg; p=0.007) and LVEF (19±7 vs. 44±12%; p=0.002) than the survivors. In addition, advanced heart failure (100% vs. 16%; p=0.002) and LGE (50% vs. 5%; p=0.04) were detected more in these subjects. CONCLUSIONS: Left ventricular non-compaction is easily overlooked at echocardiographic assessment. Congenital heart disease and WPW syndrome were relatively common in LVNC children. The prognosis of children with LVNC seemed to be better than previous studies reported, and its long-term prognosis needs to be further investigated.

Factors influencing college students' self-regulated learning in online learning environment: A systematic review.

OBJECTIVE: Drawing on the control value theory, this study aims to identify the pertinent factors of self-regulated learning in the online learning environment for college students. The analysis will inductively examine how these factors impact self-regulated learning, thereby furnishing a reference for educators and online learning platform developers to create more efficacious online learning and teaching modes. DESIGN: Systematic review. DATA SOURCES: In March 2023, electronic databases of PubMed, Web of Science, Embase, EBSCO, Cochrane and Scopus were searched, and there was no time limit for publication. REVIEW METHODS: The inclusion criteria were: (1) Includes both online learning environment and self-regulated learning variables. (2) The research object is college students. (3) The research focuses on online teaching. Assessment of risk of bias for all included studies using a mixed-methods assessment tool. RESULTS: After screening, 31 articles were finally included. Including 24 quantitative studies, 2 qualitative study and 5 mixed studies. According to the control value theory, the factors affecting self-regulated learning in online learning environment are divided into seven aspects, namely cognitive quality, motivational quality, autonomy support, goal structures and social expectations, feedback and considerations of achievement, perceived control and perceived value. CONCLUSIONS: Teachers should exercise reasonable management over the number of assignments and provide timely and supportive feedback, as well as actively create interactive learning environments to facilitate peer-to-peer communication. Developers of online learning platforms should improve the functions of the platforms according to students' needs, and provide training for teachers and students when necessary. Learners should adapt their learning status in a timely manner to realise efficient learning and improve learning outcomes.

Double-skeleton interpenetrating network-structured alkaline solid-state electrolyte enables flexible zinc-air batteries with enhanced power density and long-term cycle life.

The alkaline solid-state electrolytes have received widespread attention for their good safety and electrochemical stability. However, they still suffer from low conductivity and poor mechanical properties. Herein, we report the synthesis of double-network featured hydroxide-conductive membranes fabricated by polyvinyl alcohol (PVA) and chitosan (CS) as the double-skeletons. Then, we implanted quaternary ammonium salt guar hydroxypropyltrimonium chloride (GG) as the OH- conductor for high-performance electrochemical devices. By virtue of the unique stripe-like structure shared from the double skeleton with a high degree of compatibility and stronger hydrogen bond interactions, the polyvinyl alcohol/chitosan-guar hydroxypropyltrimonium chloride (PCG) solid-state electrolytes achieved optimal thermal stability (> 300 °C), mechanical property (∼ 34.15 MPa), dimensional stability (at any bending angle), and high ionic conductivity (13 mS cm-1) and ion mobility number (tion âˆ¼ 0.90) compared with chitosan-guar hydroxypropyltrimonium chloride (CG) and polyvinyl alcohol-guar hydroxypropyltrimonium chloride (PG) electrolyte membrane. As a proof-of-concept application, the "sandwich"-type zinc-air battery (ZAB) assembled using PCG membrane as the electrolyte realized a high open-circuit voltage (1.39 V) and an excellent power density (128 mW cm-2). Notably, in addition to its long-term cycle life (30 h, 2 mA cm-2) and stable discharge plateau (12 h, 5 mA cm-2), it could even enable a flexible ZAB (F-ZAB) to readily power light-emitting diodes (LED) at any bending angle. These merits afford the PCG membrane a promising electrolyte for improving the performance of solid-state batteries.

Modelling the case-based learning preferences of undergraduate nursing students using a discrete choice experiment in China.

PURPOSE: To investigate the preferences for case-based learning programmes among undergraduate nursing students. METHOD: A questionnaire was designed based on a discrete choice experiment, and 227 undergraduate nursing students were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULT: All attributes in our study were found to have a significant influence on undergraduate nursing students' preferences for case-based learning programmes. The students' preference for the CBL programme was influenced by the clinical internship experience and type of university. Furthermore, the most ideal scenario was found to be video case modality, unfolding delivery, provided by academic experts and clinical instructors, group size 9-11, adequate feedback, and fragmented case content. CONCLUSION: The undergraduate nursing students' preferences for case-based learning programmes were affected by the provider, case modality, modality, group size, feedback, and case content. Our results can provide useful information for nursing educators to gain insight into student preferences and formulate case-based learning programs.

Case-based learning interventions for undergraduate nursing students in a theoretical course: A review of design, implementation, and outcomes.

BACKGROUND: Case-based learning (CBL) is a contextualized learning and teaching method that can facilitate active and reflective learning to develop critical thinking and problem-solving skills. However, nursing educators have some difficulty in creating a CBL environment that matches the diverse professional nursing curriculum and students' needs, including developing relevant cases and appropriate CBL implementation processes. OBJECTIVE: To summarize the case design, implementation process, and their relationship with CBL effectiveness. METHODS: Electronic databases of PubMed, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI) and Wanfang Data (a Chinese database) were searched from inception until January 2022. Study quality was assessed using the Mixed Methods Appraisal Tool. A qualitative synthesis was then conducted to summarize the study findings. RESULTS: The systematic mixed studies review included twenty-one quantitative studies, five qualitative studies and two mixed methods studies. The case design and implementation process were indispensable parts of each study, but the application process of CBL in each study was slightly different, basically including case design, preparation, small-group interaction and exploration, collaborative efforts, teacher summary, assignment and teacher feedback. There were three themes in this review that indicate the effect of CBL on students, namely, knowledge, competence and attitude. CONCLUSION: The present review analyzes the available literature and suggests that there is no common format for the case design and CBL implementation process, but demonstrates that they are an indispensable part of each study. This review provides conceptual procedures for nurse educators to design and implement CBL in nursing theoretical courses to improve the effectiveness of CBL.

Corrigendum: Tilianin extracted from Dracocephalum moldavica L. induces intrinsic apoptosis and drives inflammatory microenvironment response on pharyngeal squamous carcinoma cells via regulating TLR4 signaling pathways.

[This corrects the article DOI: 10.3389/fphar.2020.00205.].

Proteomic analysis implicates that postovulatory aging leads to aberrant gene expression, biosynthesis, RNA metabolism and cell cycle in mouse oocytes.

BACKGROUND: In mammals, oocytes display compromised quality after experiencing a process of postovulatory aging. However, the mechanisms underlying are not yet fully understood. Here, we portrayed a protein expression profile of fresh and aging metaphase II (MII) mouse oocytes by means of four-dimensional label-free quantification mass spectrometry (4D-LFQ). RESULTS: The analysis of 4D-LFQ data illustrated that there were seventy-six differentially expressed proteins (DEPs) between two groups of MII stage oocytes. Fifty-three DEPs were up-regulated while twenty-three DEPs were down-regulated in the MII oocytes of the aging group, and Gene Ontology (GO) analysis revealed that these DEPs were mainly enriched in regulation of gene expression, biosynthesis, RNA metabolism and cell cycle. Our detailed analysis revealed that the expression of proteins that related to gene expression processes such as transcription, translation, post-translational modifications and epigenome was changed; the relative protein expression of RNA metabolic processes, such as RNA alternative splicing, RNA export from nucleus and negative regulation of transcription from RNA polymerase II promoter was also altered. CONCLUSION: In conclusion, we identified considerable DEPs and discussed how they agreed with previous researches illustrating altered protein expression associated with the quality of oocytes. Our research provided a new perspective on the mechanisms of postovulatory aging and established a theoretical support for practical methods to control and reverse postovulatory aging.

Concurrent Primary Aldosteronism and Renal Artery Stenosis: An Overlooked Condition Inducing Resistant Hypertension.

To explore the clinical features of coexisting primary aldosteronism (PA) and renal artery stenosis (RAS), we retrospectively analyzed records from 71 patients with PA with RAS and a control group of 121 patients with PA without RAS. Aldosterone-to-renin concentration ratio tests and computerized tomography (CT) scanning of the adrenal and renal arteries were routinely conducted to screen for PA and RAS. Color Doppler flow and/or magnetic resonance imaging were used as substitute testing of patients for whom CT was contraindicated. Standard percutaneous renal arteriography (PTRA) was considered for patients with RAS exceeding 70% based on non-invasive tests and for those without PTRA contraindications. The patients with PA with RAS were further divided into severe (RAS>70%) and moderate (50% < RAS <70%) RAS groups. The prevalence of RAS among PA patients was 6.9% (71/1,033), including 3.2% (33/1,033) with severe RAS. Compared with the PA without RAS group, the severe RAS group showed higher levels of systolic blood pressure (SBP) (171.82 ± 18.24 vs. 154.11 ± 18.96 mmHg; P < 0.001) and diastolic BP(DBP) (110.76 ± 15.90 vs. 91.73 ± 12.85 mmHg; P < 0.001) and prevalence of resistant hypertension (RH) (90.9 vs. 66.9%; P = 0.008), whereas the moderate RAS group merely showed higher DBP (98.63 ± 14.90 vs. 91.73 ± 12.85 mmHg; P = 0.006). The direct renin concentrations (DRCs) (5.37 ± 3.94 vs. 3.71 ± 2.10 µU/mL; P < 0.001) and false-negative rate (33.8 vs. 3.3%; P < 0.01) of PA screening tests were significantly higher in the PA with RAS group than in the control group, but only in severe RAS group, in subgroup analysis. Among patients who underwent successful treatment for severe RAS, mean DRC decreased from 11.22 ± 9.10 to 3.24 ± 2.69 µIU/mL (P < 0.001). Overall, the prevalence of RH decreased from 81.7 to 2.8% (P < 0.001) when both PA and RAS were treated with standard methods. PA with concurrent severe RAS is a condition that induces RH. PA can be easily missed in patients with coexisting RAS. RAS patients with RH after successful revascularization for RAS should be evaluated for coexisting PA.

Implication of a novel truncating mutation in titin as a cause of autosomal dominant left ventricular noncompaction.

BACKGROUND: Mutation in the titin gene (TTN) in left ventricular noncompaction (LVNC) has been reported with a highly heterogeneous prevalence, and the molecular mechanisms underlying the pathogenesis of TTN gene mutation are uncharacterized. In the present study, we identified a novel TTN mutation in a pedigree with LVNC and investigated the potential pathogenic mechanism by functional studies. METHODS: The whole-genome sequencing with linkage analysis was performed in a 3-generation family affected by autosomal dominant LVNC cardiomyopathy. The clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) technology was used to establish novel truncating mutation in TTN in a rat cardiomyoblast H9C2 cell line in vitro, in which functional studies were carried out and characterized in comparison to its wild-type counterpart. RESULTS: A novel truncating mutation TTN p. R2021X was identified as the only plausible disease-causing variant that segregated with disease among the five surviving affected individuals, with an interrogation of the entire genome excluding other potential causes. Quantitative reverse transcription-polymerase chain reaction and cellular immunofluorescence supported a haploinsufficient disease mechanism in titin truncation mutation cardiomyocytes. Further functional studies suggested mitochondrial abnormities in the presence of mutation, including decreased oxygen consumption rate, reduced adenosine triphosphate production, impaired activity of electron translation chain, and abnormal mitochondrial structure on electron microscopy. Impaired autophagy under electron microscopy accompanied with activation of the Akt-mTORC1 signaling pathway was observed in TTN p. R2021X truncation mutation cardiomyocytes. CONCLUSIONS: The TTN p. R2021X mutation has a function in the cause of a highly penetrant familial LVNC. These findings expand the spectrum of titin's roles in cardiomyopathies and provide novel insight into the molecular basis of titin-truncating variants-associated LVNC.

Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.

Objective: Liddle syndrome (LS) is a monogenic hypertension consistent with autosomal dominant inheritance, often with early onset high blood pressure in childhood or adolescence. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the long-term outcomes of tailored treatment with amiloride. Methods: To explore the pathogenicity of candidate variant reported in 2015 by our team, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary (CHO) cells using patch clamp technique. Participants were followed up for 7 years after tailored treatment with amiloride. Results: A nonsense variant was detected in six members, two of whom were pediatric patients. This mutation resulted in a termination codon at codon 572, truncating the Pro-Pro-Pro-X-Tyr motif. The mutant epithelial sodium channels displayed higher amiloride-sensitive currents than the wild-type channels (P < 0.05). Tailored treatment with amiloride achieved ideal blood pressure control in all patients with normal cardiorenal function, and no adverse events occurred during follow-up. Conclusion: We found the pathogenicity of a nonsense SCNN1G mutation (p.Glu571*) with enhanced amiloride-sensitive currents in a LS family with young patients. Tailored treatment with amiloride may be an effective strategy for the long-term control of blood pressure and protection from target organ damage or cardiovascular events, including children and youth patients with LS.

A novel missense mutation in obscurin gene in a Chinese consanguineous family with left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is an increasingly recognised cardiomyopathy of which a significant percentage are genetic in origin. The purpose of the present study was to identify potential pathogenic mutation leading to disease in a Chinese LVNC family. METHODS: A 3-generation family affected by LVNC was recruited. Clinical assessments were performed on available family members, with clinical examination, ECG, echocardiography and cardiac MRI. The proband (I-2), the proband's daughter (II-1, affected) and mother (III-1, unaffected) were selected for WGS. Sanger sequencing were performed in all of the 4 surviving family members. RESULTS: Combined whole genome sequencing with linkage analysis identified a novel missense mutation in the giant protein obscurin (OBSCN NM_001098623, c.C19063T), as the only plausible disease-causing variant that segregates with disease among the four surviving individuals, with interrogation of the entire genome excluding other potential causes. This c.C19063T missense mutation resulted in p.R6355W in the encoded OBSCN protein. It affected a highly conserved residue in the C terminus of the obscurin-B-like isoform between the PH and STKc domains, which was predicted to affect the function of the protein by different bioinformatics tools. CONCLUSIONS: Here we present clinical and genetic evidence implicating the novel R6355W missense mutation in obscurin as the cause of familial LVNC. This expands the spectrum of obscurin's roles in cardiomyopathies. It furthermore highlights that rare obscurin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. This study also provided new insights into the molecular basis of OBSCN mutation positive LVNC.

Corrigendum: Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.

[This corrects the article DOI: 10.3389/fped.2022.887214.].

Severe right ventricular hypertrophy in hypertrophic cardiomyopathy: Serious symptoms, complex surgical procedures, and poor prognosis in Fuwai Hospital.

OBJECTIVE: Severe right ventricular hypertrophy (SRVH) in hypertrophic cardiomyopathy (HCM) is rare. We studied the clinical characteristics and prognosis of 36 patients with HCM and SRVH in a Chinese cohort. METHODS: Patients with HCM and SRVH were enrolled between 2013 and 2017. The clinical characteristics, treatment therapies, and clinical outcomes of the 36 patients were retrospectively studied and compared with those of 128 patients without SRVH. RESULTS: Patients in the group with SRVH were younger than those in the group without SRVH (27.58±15.09 years vs 40.34±13.21 years, respectively; p<0.001). Patients with SRVH had more serious clinical symptoms and a higher New York Heart Association functional class than those without SRVH. Most patients in the group with SRVH exhibited diffuse RV hypertrophy, and 13 patients presented with biventricular outflow tract obstruction. Maximal left ventricular (LV) wall thickness (27.29±7.95 mm vs 24.33±5.85 mm, respectively; p=0.027) and LV outflow tract gradient (80.83±24.41 mm Hg vs 42.3±5.7 mm Hg, respectively; p=0.000) were significantly greater in patients with SRVH than in those without SRVH. A total of 30 patients in the group with SRVH underwent surgical correction. During a median follow-up period of 48 months, six patients with SRVH reached primary clinical endpoints (four sudden cardiac deaths, one heart failure-related death, and one heart transplantation), whereas only two deaths occurred in the patients without SRVH. CONCLUSION: We conclude that patients with HCM and SRVH exhibit serious symptoms and have complex surgical requirements and poor clinical outcomes.