Comprehensive analysis of POLH-AS1 as a prognostic biomarker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. METHODS: In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman's rank correlation analysis to examine the association between POLH-AS1 expression and the tumor's immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. CONCLUSIONS: POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

Shared atypical spontaneous brain activity pattern in early onset schizophrenia and autism spectrum disorders: evidence from cortical surface-based analysis.

Schizophrenia and autism spectrum disorders (ASD) were considered as two neurodevelopmental disorders and had shared clinical features. we hypothesized that they have some common atypical brain functions and the purpose of this study was to explored the shared brain spontaneous activity strength alterations in early onset schizophrenia (EOS) and ASD in the children and adolescents with a multi-center large-sample study. A total of 171 EOS patients (aged 14.25 ± 1.87), 188 ASD patients (aged 9.52 ± 5.13), and 107 healthy controls (aged 11.52 ± 2.82) had scanned with Resting-fMRI and analyzed surface-based amplitude of low-frequency fluctuations (ALFF). Results showed that both EOS and ASD had hypoactivity in the primary sensorimotor regions (bilateral primary and early visual cortex, left ventral visual stream, left primary auditory cortex) and hyperactivity in the high-order transmodal regions (bilateral SFL, bilateral DLPFC, right frontal eye fields), and bilateral thalamus. EOS had more severe abnormality than ASD. This study revealed shared functional abnormalities in the primary sensorimotor regions and the high-order transmodal regions in EOS and ASD, which provided neuroimaging evidence of common changes in EOS and ASD, and may help with better early recognition and precise treatment for EOS and ASD.

[Intervention effect of narrative therapy on non-suicidal self-injury in adolescents with depressive disorder: a prospective randomized controlled study]. / å™äº‹æ²»ç–—å¯¹é’å°‘å¹´æŠ‘éƒç—‡æ‚£è€ éžè‡ªæ€æ€§è‡ªä¼¤çš„å¹²é¢„æ•ˆæžœï¼šä¸€é¡¹å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the intervention effect of narrative therapy on non-suicidal self-injury (NSSI), as well as anxiety and depression symptoms in adolescents with depressive disorder. METHODS: Sixty adolescents with depressive disorder and NSSI were randomly assigned to either the intervention group or the control group using coin flipping. The control group received conventional psychological support, while the intervention group received individual narrative therapy in addition to the conventional psychological support (twice a week, 60 minutes per session, for a total of 3 weeks). Assessment of treatment efficacy was conducted using the Adolescent Self-Harm Questionnaire, Children's Depression Inventory, and Children's Anxiety and Mood Scale before the intervention, at the end of the intervention, and one month after the intervention for both groups. RESULTS: A total of 26 adolescents in the intervention group and 29 adolescents in the control group completed the entire study. At the end of the intervention and one month after the intervention, the intervention group showed a significant reduction in the NSSI frequency score, NSSI level, anxiety score, and depression score compared to before the intervention (P<0.017). Moreover, at the end of the intervention and one month after the intervention, the intervention group exhibited significantly lower NSSI frequency score, NSSI severity score, NSSI level, anxiety score and depression score compared to the control group (P<0.05). CONCLUSIONS: Narrative therapy is effective in reducing NSSI frequency and alleviating NSSI severity, as well as anxiety and depression symptoms in adolescents with depressive disorder.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Cesium acetate-assisted crystallization for high-performance inverted CsPbI3perovskite solar cells.

Efficient inverted (p-i-n) type CsPbI3perovskite solar cells (PSCs) have revealed promising applications due to their excellent thermal and photostability. Regulating the nucleation and crystallization of perovskite film is an important route to improving the performance of CsPbI3PSCs. Herein, we explored cesium acetate (CsAc) as additive to manipulate the crystallization process of CsPbI3perovskite films. By involving in the intermediate phase DMA1-xCsxPbI3-yAcyof perovskite, the pseudo-halide acetate (Ac-) can retard the ion exchange reaction between DMA+and Cs+, leading to a perovskite with dense morphology, low defect density, and a long carrier lifetime. As a result, the optimal CsPbI3PSCs yielded a high power conversion efficiency of 18.3%. Moreover, the encapsulated devices showed excellent operational stability and the devices retained their initial performance following 500 h of operation at the maximum power point under one-sun illumination in ambient conditions.

Prevalence and associated factors of minimally invasive facial cosmetic surgery in Chinese college students.

BACKGROUND: Minimally invasive facial cosmetic surgery (MIFCS) is becoming more and more popular and acceptable in Chinese young people, and it influences people in many aspects. However, there is little research on the associations between MIFCS and psychopathology in Chinese college students. The purpose of this study was to identify the prevalence of MIFCS and its associated factors among Chinese college students. METHODS: A cross-sectional design was applied in this study. A total of 8089 students completed an online questionnaire on demographic data, depressive symptoms (Self-Rating Depression Scale), anxiety symptoms (Self-Rating Anxiety Scale) and MIFCS. Logistic regression was used to identify independent factors associated with MIFCS. RESULTS: The prevalence of MIFCS in Chinese college students was 2.7% (221/8098). Students with MIFCS were more likely to be from urban areas, from a single child household, experience depression or anxiety and have a history of smoking (all p < 0.05). They were also less likely to be right-handed or have a good relationship with father or mother (all p < 0.05). Binary logistic regression showed that older age (OR,1.162; 95%CI [1.061,1.273]), female sex (OR,1.837; 95%CI [1.352, 2.497]), community (urban) (OR,0.601; 95%CI [0.441,0.818]), right-handedness (OR,0.668; 95%CI [0.454,0.985]), depressive symptoms (OR, 4.708; 95%CI [1.690,13.112]), family income (30,000-70,000 yuan per year) (OR,0.572; 95%CI [0.403,0.812]) and smoking (OR,1.571; 95%CI [1.09,2.423]) were independently associated with MIFCS. CONCLUSIONS: Minimally invasive facial cosmetic surgery (MIFCS) is very common in Chinese college students, indicating the importance of paying attention to MIFCS. This study provides valuable evidence for college counselors and doctors in the cosmetic department to provide better and healthier services to students who undergo MIFCS, especially those with depressive symptoms.

MASR: A novel monitoring method coupled with interpretation platform for near-term management in thermal stratified reservoirs.

Good water quality is critical to public health and aquatic ecological security of global reservoirs. In stratified reservoirs, increasing near-term management demands foster extremely high monitoring and forecasting needs. In this study, a management assistant for stratified reservoirs (MASR) was developed, including a wave-driven monitoring platform and interpretation platform for multiple reservoir water quality variables. The wave-driven platform can adapt to the characteristics of water level changes and transmit the monitoring data through a mobile network to the reservoir manager, which are processed by the interpretation platform in real time for near-term management. After several months of application, MASR monitored 1237 groups of valid profile water quality data with an acceptable error, which showed a strong capacity for capturing the water quality dynamics in a stratified reservoir. The effective identification of thermal stratification structures and anoxic zones can help managers to design withdrawal schemes for reservoirs. Moreover, the prediction of algae state based on the back propagation (BP) neural network provided the basis for making operation plans to proactively control algae blooms. Our study provides an economical and convenient solution for stratified reservoirs to address near-term management issues.

Two-Terminal Perovskite-Based Tandem Solar Cells for Energy Conversion and Storage.

The organic-inorganic hybrid perovskite solar cells present a rapid improvement on power conversion efficiency from 3.8% to 25.5% in the past decades. Owing to the tuneable bandgaps, low-cost, and ease of fabrication, perovskites become ideal candidate materials for fabricating tandem solar cells, especially for efficient and high-voltage monolithic two-terminal devices. In this review, an overview of recent advances in various monolithic perovskite-based tandem solar cells with a focus on the key challenges is provided. Subsequently, the recombination layer materials, construction of wide-bandgap perovskite layer, stability of narrow-bandgap, and current matching principle in tandems are highlighted in order to optimize the output voltage and conversion efficiency of tandem solar cells. Finally, the recent progress is summarized with a focus on potential applications of tandem solar cells for energy conversion and storage, including hydrogen production by water splitting, CO2 reduction, supercapacitors, and rechargeable batteries, benefiting from the adjustable output voltage of tandem solar cells. It is hoped that this work can offer a feasible strategy to explore more possibilities for fabricating new two-terminal tandem solar cells with high voltage and high conversion efficiency for energy conversion and storage.

Crystalline Multi-Metallic Compounds as Host Materials in Cathode for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) battery is one of the most promising next-generation rechargeable batteries. Lots of fundamental research has been done for the problems during cycling like capacity fading and columbic efficiency reducing owing to severe diffusion and migration of polysulfide intermediates. In the early stage, a wide variety of carbon materials are used as host materials for sulfur to enhance electrical conductivity and adsorb soluble polysulfides. Beyond carbon materials, metal based polar compounds are introduced as host materials for sulfur because of their strong catalytic activity and adsorption ability to suppress the shuttle effect. In addition, relatively high density of metal compounds is helpful for increasing volumetric energy density of Li-S batteries. This review focuses on crystalline multi-metal compounds as host materials in sulfur cathodes. The multi-metal compounds involve not only transition metal composite oxides with specific crystalline structures, binary metal chalcogenides, double or complex salts, but also the metal compounds doped or partially substituted by other metal ions. Generally, for the multi-metal compounds, microstructure and morphologies in micro-nano scale are very significant for mass transfer in electrodes; moreover, adsorption and catalytic ability for polysulfides make fast kinetics in the electrode processes.

Diurnal variation of transitory starch metabolism is regulated by plastid proteins WXR1/WXR3 in Arabidopsis young seedlings.

Transitory starch is the portion of starch that is synthesized during the day in the chloroplast and usually used for plant growth overnight. Here, we report altered metabolism of transitory starch in the wxr1/wxr3 (weak auxin response 1/3) mutants of Arabidopsis. WXR1/WXR3 were previously reported to regulate root growth of young seedlings and affect the auxin response mediated by auxin polar transport in Arabidopsis. In this study the wxr1/wxr3 mutants accumulated transitory starch in cotyledon, young leaf, and hypocotyl at the end of night. WXR1/WXR3 expression showed diurnal variation. Grafting experiments indicated that the WXRs in root were necessary for proper starch metabolism and plant growth. We also found that photosynthesis was inhibited and the transcription level of DIN1/DIN6 (Dark-Inducible 1/6) was reduced in wxr1/wxr3. The mutants also showed a defect in the ionic equilibrium of Na+ and K+, consistent with our bioinformatics data that genes related to ionic equilibrium were misregulated in wxr1. Loss of function of WXR1 also resulted in abnormal trafficking of membrane lipids and proteins. This study reveals that the plastid proteins WXR1/WXR3 play important roles in promoting transitory starch degradation for plant growth over night, possibly through regulating ionic equilibrium in the root.

The effects of turbulence on phytoplankton and implications for energy transfer with an integrated water quality-ecosystem model in a shallow lake.

Turbulence has significant influences on the growth rate and community structure of phytoplankton in large shallow lakes. Phytoplankton in moving water may be influenced by turbulence and nutrient concentration gradients on a short time scale. To assess this issue, our research used an ensemble water quality and ecological model by internally coupling the three-dimensional hydrodynamic model, the Environmental Fluid Dynamics Code (EFDC), and the one-dimensional ecosystem model, PCLake. The results showed that turbulence dramatically inhibited phytoplankton growth, while nutrients had the opposite effect. In addition, turbulence was the key factor contributing to phytoplankton growth. However, the effects of turbulence on phytoplankton correlated with nutrient concentrations. For lower nutrient concentrations, phytoplankton growth was controlled by nutrients. Logistic regression models were established with the modeled chlorophyll a, total nitrogen (TN), total phosphorus (TP) and turbulent kinetic energy (Ke). The results also showed that turbulence could improve nutrient uptake by phytoplankton, especially at low nutrient levels. The effects of turbulence on phytoplankton may imply that energy transfer occurs between water turbulence and phytoplankton. Our study will provide insight into management and remediation strategies of ecosystems based on energy processes in the future.

Interleukin 21 Reinvigorates the Antiviral Activity of Hepatitis B Virus (HBV)-Specific CD8+ T Cells in Chronic HBV Infection.

BACKGROUND: Strategies that target functional recovery of exhausted hepatitis B virus (HBV)-specific CD8+ T cells are beneficial for viral control, but the potential for interleukin 21 (IL-21) to rescue CD8+ T-cell function is not well understood. METHODS: We investigated the effect of IL-21 on CD8+ T-cell responses by phenotypic and functional analysis of samples from patients with chronic HBV infection and a mouse model with HBV expression. RESULTS: IL-21 promoted the proliferative capacity of HBV-specific CD8+ T cells and down-regulated expression of the inhibitory receptors programmed death 1 and T-cell immunoglobulin domain and mucin domain 3. Additionally, IL-21 boosted the production of interferon-γ, granzyme B, and CD107a in HBV-specific CD8+ T cells and enhanced the cytolytic activity of CD8+ T cells against HepG2.2.15 cells. Notably, an HBV mouse model established from IL-21 receptor knockout mice showed significantly decreased frequency of HBV-specific CD8+ T cells and increased levels of serum hepatitis B surface antigen (HBsAg). Meanwhile, administration of recombinant mouse IL-21 in an HBV mouse model established from wild-type mice resulted in enhanced functionality of HBV-specific CD8+ T cells and accelerated HBsAg clearance. CONCLUSIONS: IL-21 enhances the antiviral effect of HBV-specific CD8+ T cells, suggesting that it may contribute to viral clearance in chronic HBV infection.

Young seedlings adapt to stress by retaining starch and retarding growth through ABA-Dependent and -independent pathways in Arabidopsis.

The metabolism of starch, the major resource of carbohydrates and an essential determinant of plant fitness in plants, often exhibits plasticity in response to challenging environmental conditions. Previous study of leaf starch turnover under abiotic stresses documented conflicting patterns. To understand this discrepancy and examine the process in more detail, we grew Arabidopsis seedlings under a series of typical stress conditions, observed and quantified leaf starch content at different time. By electron microscope, iodine staining and starch quantification, we confirm that short-term (<8 h) stress treatments, such as osmotic stress, high salinity, caused rapid starch decrease during the night while long-term (>56 h) stresses increased starch content significantly. Exogenous abscisic acid (ABA) induced similar effects to the abiotic stresses. Comparison of the starch content in wild type (WT) and the ABA receptor quadruple mutant pyr1;pyl1;pyl2;pyl4 suggests that the stress-induced starch turnover change is also mediated by ABA-independent pathways. In addition, more energy supply caused severer growth defect under stress conditions. And the transcription levels of both starch biosynthesis enzymes (APL1 and APL3) and starch degradation enzymes (SEX1, SEX4, BAM1 and BAM3) exhibited differential increase under long-term stresses. Taken together, our data strongly suggest that young seedlings adapt to stress by retaining starch and retarding growth through both ABA-dependent and -independent pathways.

Similarity Theory of Withdrawn Water Temperature Experiment.

Selective withdrawal from a thermal stratified reservoir has been widely utilized in managing reservoir water withdrawal. Besides theoretical analysis and numerical simulation, model test was also necessary in studying the temperature of withdrawn water. However, information on the similarity theory of the withdrawn water temperature model remains lacking. Considering flow features of selective withdrawal, the similarity theory of the withdrawn water temperature model was analyzed theoretically based on the modification of governing equations, the Boussinesq approximation, and some simplifications. The similarity conditions between the model and the prototype were suggested. The conversion of withdrawn water temperature between the model and the prototype was proposed. Meanwhile, the fundamental theory of temperature distribution conversion was firstly proposed, which could significantly improve the experiment efficiency when the basic temperature of the model was different from the prototype. Based on the similarity theory, an experiment was performed on the withdrawn water temperature which was verified by numerical method.

Effect of flow rate of side-type orifice intake on withdrawn water temperature.

Side-type orifice intake is a type of selective withdrawal facility used in managing reservoirs to mitigate the negative effects of low-temperature water. Based on the temperature data of a thermal stratified reservoir in China, an experiment was conducted in flume to study the influence of intake flow rate on withdrawn water temperature with different temperature distributions. Results indicated that withdrawn water temperature changed with different flow rates. The temperature change was determined by the water temperature gradients above and below the intake, whereas the change trend of temperature depended on the difference between the water temperature gradient above and below the intake. We likewise proposed a new equation with which the withdrawn water temperature of a thermal stratified reservoir using a side-type orifice could be calculated. These findings could be directly applied to the design and operation of side-type orifice intake in thermal stratified reservoirs.

Oxygen evolution and its drivers in a stratified reservoir: A supply-side perspective for informing hypoxia alleviation strategies.

Hypoxia in stratified waters greatly threatens aquatic ecology and societal development owing to enhanced nutrient discharge and increasing global temperature. Current research predominantly alleviates hypoxia by reducing dissolved oxygen (DO) consumption or conducting hypolimnetic oxygenation, yet their implementation has encountered bottlenecks. Therefore, this study explores the potential of increasing the inherent DO supplies in stratified reservoirs to mitigate hypoxia. High-frequency in situ observations and massive modeling experiments are integrated to discern the DO supply mode and the dominant driver of DO evolution. Results indicate that periodic thermodynamic conditions determine the DO supply relationships between oxygen sources (inflow carriage, reaeration, and photosynthesis) for different water layers. Thermal stratification causes the hypolimnion to rely mostly on the inflow for DO supply, leading to a fragile budget prone to hypoxia. However, episodic hydrodynamic events (turnover, wind stir, density current, and flood) can promote DO supply and inhibit hypoxia. Temperature and DO regimes are primarily driven by outflow conditions, followed by inflow and meteorology conditions. Furthermore, hypolimnetic hypoxia can be regulated by altering inflow volume, outflow volume, and outlet elevation. These findings highlight the importance of longitudinal solute exchange in DO evolution in stratified reservoirs, providing a basis for alleviating hypoxia through cascade reservoir operations.

Synergistic Interfacial Optimization for High-Sulfur-Content All-Solid-State Lithium-Sulfur Batteries.

Improving the sulfur content in the cathode is essential for achieving high-energy-density all-solid-state lithium-sulfur batteries (ASSLSBs). However, the complex multiinterfaces, akin to the short wooden planks that consist of the cask, severely limit the performance of ASSLSBs with high sulfur content. Since singular approaches fail to optimize these interfaces simultaneously, we propose a synergistic approach using a dual-doped sulfide solid electrolyte (Y2S3 and LiI) and an SbSn alloy sulfur host in this work. The incorporation of Y2S3 in the solid electrolyte serves to improve the electrolyte-electrolyte interfaces and enhance the ionic conductivity, while the inclusion of LiI helps stabilize the electrolyte-anode interface and suppress dendrite formation. Meanwhile, the SbSn alloy sulfur host facilitates the transfer of Li+ at the electrolyte-cathode interfaces. Consequently, the solid-solid interfaces are significantly improved, leading to impressive specific capacities in ASSLSBs with high sulfur content (>44% in the cathode composite) at room temperature (1163.5 mAh g-1) and at 60 °C (1408.7 mAh g-1) during the 50th cycle at 0.05C. This work presents a promising strategy for achieving practical high-performance ASSLSBs.

Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most common subtype among African and African Americans, primarily caused by pathogenic variants in the OCA2 (HGNC ID: 8101) gene. In this study, we presented a Chinese family with OCA and reported two novel variants in the OCA2 gene. METHODS: Whole-exome sequencing (WES) was performed to identify pathogenic variants in the proband. The candidate variants were subsequently validated using Sanger sequencing and QPCR assay. Additionally, bioinformatics analyses were employed to predict the deleteriousness and conservation of the identified mutations. RESULTS: In the 16-year-old male proband, two novel compound heterozygous OCA2 variants, NM_000275.3: c.1640T>G (NP_000266.2: p.L547R) and an exons 10-19 deletion variant, were identified. Meanwhile, a reported heterozygous variant c.1441G>A/p.A481T (NM_000275.3, NP_000266.2) in the OCA2 gene was also found in the proband. Sanger sequencing confirmed that the two variants c.1441G>A/p.A481T and c.1640T>G/p.L547R were inherited from his father. Moreover, qPCR assay revealed that the exons 10-19 deletion was inherited from the mother, his sister also carried this variant. Fortunately, the variant was not detected in the amniotic fluid of the proband's sister. Multiple online bioinformatics tools predicted the variant c.1640T>G to be damaging, leading to the replacement of a highly conserved leucine with an arginine. The gross exon 10-19 deletion in the OCA2 gene resulted in a truncated, non-functional protein losing the 3-9 transmembrane α-helices domains. According to the American College of Medical Genetics and Genomics classification, these three variants in the OCA2 gene were evaluated as likely pathogenic. CONCLUSION: This study has identified two novel compound variants in the OCA2 gene and a previously reported variant in a Chinese family with OCA. By expanding the mutation spectrum of the OCA2 gene, our findings contribute to a better understanding of the genetic basis of OCA.

A novel CHD7 variant in a chinese family with CHARGE syndrome.

OBJECTIVE: CHARGE syndrome is a rare autosomal dominant (AD) multi-system disorder with a broad and variable clinical manifestation and occurs in approximately 1/10,000 newborns in the world. Mutations in the CHD7 gene are the genetic cause of over 90% of patients with typical CHARGE syndrome. The present study reported a novel variant in the CHD7 gene in a Chinese family with an abnormal fetus. METHODS: Routine prenatal ultrasound screening showed fetal heart abnormality and left foot varus. Chromosomal microarray analysis (CMA) and fetus-parent whole-exome sequencing (trio-WES) were performed to determine the genetic cause of the fetus. The candidate variant was further verified using Sanger sequencing. RESULTS: CMA analysis revealed normal results. However, WES analysis identified a de novo heterozygous variant of c.2919_2922del (NM_017780.4) on exon 11 of CHD7 gene, resulting in a premature truncation of the CHD7 protein (p.Gly975*). The variant was classified as Pathogenic (PVS1 + PS2_Moderate + PM2_Supporting) based on the ACMG guidelines. Combined with the clinical phenotype of fetal heart abnormalities, it was confirmed CHARGE syndrome. CONCLUSION: We identified a novel heterozygous variant c.2919_2922del in CHD7 of a Chinese fetus with CHARGE syndrome, enriching the genotype-phenotype spectrum of CHD7. These results suggest that genetic testing could help facilitate prenatal diagnosis of CHARGE syndrome, thus promoting the appropriate genetic counseling.