ZnS spheres assembled from nanoparticles confined in bagasse-based carbon nanosheets for enhanced potassium storage.

Transition metal zinc sulfide (ZnS) is a promising anode material for potassium ion batteries due to its rich abundance and high capacity (conversion/alloy dual mechanism), while still suffering the drawbacks of sluggish kinetics process and structural degradation, which restrict its practical application. Herein, ZnS spheres assembled from nanoparticles embedded in carbon nanosheets (ZnS/C@C) were synthesized with alkali-activated agricultural waste bagasse as the carbon precursor. The removal of lignin and hemicellulose by pre-treatment of bagasse with alkali solutions opens ionic diffusion channels and promotes adsorption of Zn2+by bagasse, which is crucial for the growth of ZnS in bagasse sheets and the suppression of ZnS particle size during hydrothermal processes. Benefiting from the synergistic effects between robust embedded structure, carbon conductive network and the nanoscale nature of ZnS, the ZnS/C@C exhibited enhanced performance with high capacity (374.7 mA h g-1at 0.2 A g-1) and rate performance (195.9 mA h g-1at 2.0 A g-1). Kinetic studies further demonstrate that ZnS/C@C electrodes possess faster K+transport kinetics and lower interfacial impedance. This work provides a reference for the construction of robust embedded carbon composite structures based on surface control of agricultural waste.

Association of Elevated Cord Blood Oxidative Stress Biomarkers with Neonatal Outcomes in Mothers with Pre-Eclampsia: A Case-Control Study.

OBJECTIVES: The objective of this study was to determine the relationship between the levels of stress biomarkers in cord blood and pre-eclampsia (PE) in a hospital-based population of pregnant patients and evaluate the effects on pregnancy outcomes. DESIGN: This was an observational, case-control study. Participants/Materials, Setting, Methods: This case-control study included 282 patients with severe PE and 534 women with normal pregnancy. The umbilical cord was collected at delivery and tested for malonaldehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, and homocysteine (Hcy) analysis. We performed a univariate general linear regression model analysis to control potential confounders and determined the underlying influencing factors for high MDA and ROS. A receiver operating characteristic curve analysis was conducted to determine the cutoff values for identifying severe PE. Further, the severe PE group was divided into the low- or high-MDA and low- or high-ROS subgroups according to the cutoff values. Finally, we created logistic regression models to estimate the adjusted odds ratio for each perinatal outcome in the high-MDA and high-ROS subgroup. RESULTS: The levels of MDA and ROS levels were higher in women with severe PE than in normotensive pregnant patients. However, when adjusted for cord blood Hcy levels, the difference was insignificant. Additionally, both MDA (r = 0.359, p < 0.001) and ROS (r = 0.473, p < 0.001) were positively correlated with the cord blood Hcy level. The areas under the curve of MDA and ROS levels were 0.65 (95% confidence interval [CI]: 0.60-0.69) and 0.88 (95% CI: 0.86-0.90), respectively. Higher MDA and ROS levels were associated with increased risks of a low Apgar score, admission to the NICU, and assisted ventilation for the newborn. LIMITATIONS: The study design led to the exclusion of several participants. CONCLUSIONS: Increased levels of oxidative stress markers in the cord blood might be significantly associated with negative effects on newborns. High levels of Hcy in the cord blood might be associated with elevated MDA and ROS concentrations in women with severe PE.

[Identification of a novel TSC2 gene variant in a patient with tuberous sclerosis complex].

OBJECTIVE: To explore the genetic basis for a patient diagnosed with tuberous sclerosis complex (TSC). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect potential variant, and the result was verified by Sanger sequencing. RESULTS: The patient was found to harbor a heterozygous c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene. The same variant was not found in his unaffected parents and 100 unrelated healthy controls. Based on the American College of Medical Genetics and Genomics guidelines, the variant was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION: The novel c.1053delG (p.Glu352SerfsX10) frameshifting variant of the TSC2 gene probably underlay the TSC in this patient.

Association between serum homocysteine level and unexplained infertility in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): A retrospective, hospital-based, case-control study.

BACKGROUND: Lower serum homocysteine (Hcy) levels are found to correlate with a better chance of clinical pregnancy and better embryo grades in assisted reproductive technology (ART). However, there is little knowledge on the association between Hcy level and unexplained infertility until now. METHODS: A total of 388 infertile women undergoing IVF/ICSI treatments were recruited, including 129 women with unexplained causes (case group) and 259 women with known causes (control group), and the case group was further divided into subgroups A (≤8 µmol/L), B (>8 and <15 µmol/L), and C (≥15 µmol/L) based on the serum Hcy level. The associations between serum Hcy level and IVF/ICSI pregnancy outcomes were examined in infertile women with unknown causes. RESULTS: A significantly higher serum Hcy level was measured in the case group than in the control group (P = .008). Subgroup analysis revealed a significant difference in the total number of oocytes retrieved among subgroups A, B, and C (P = .031), and no significant difference was seen among these three groups in terms of age, BMI, E2 level on the hCG day, number of M-II oocytes, number of fertilized oocytes, or total number of high-quality embryos (P > .05). Spearman correlation analysis revealed a negative correlation between serum Hcy level and total number of oocytes retrieved (r = -.406, P = .019). Univariate and multivariate linear regression analyses revealed that serum Hcy level had no correlations with any IVF/ICSI outcomes. CONCLUSION: Serum Hcy level has no associations with IVF/ICSI pregnancy outcomes.

Variation in ICE1 Methylation Primarily Determines Phenotypic Variation in Freezing Tolerance in Arabidopsis thaliana.

Cold stress is a major abiotic factor plants face during their life cycle. Although plants often exhibit phenotypic variation in cold tolerance, the underlying mechanism remains poorly understood. In the present study, the 50% lethal temperature (LT50) values of 37 Arabidopsis thaliana accessions at latitudes from 15° to 58° ranged from -13.2°C to -4.9°C and were closely correlated with the cold climates of the collection sites. According to a methylation analysis of all C-repeat (CRT)-binding factor (CBF) pathway genes, the coding and promoter regions of AtICE1, a regulator of CBF genes, exhibited the greatest variability in methylation levels among the accessions and included 5-122 methylated cytosine residues. In contrast, unmethylated or only slightly methylated genes in the CBF pathway showed little variation among the accessions. According to a gene expression analysis of four selected A. thaliana populations with distinct methylation patterns, except for the down-regulated gene AtCBF2, the expression levels of all members of the CBF pathway were negatively correlated with AtICE1 gene methylation levels. Treatment of the four A. thaliana populations with the DNA methylation inhibitory reagent 5-azacytidine resulted in a 30.0-78.3% enhancement of freezing tolerance and decreases in LT50 values of approximately 1.9-3.6°C. Similar effects were observed in drm2 mutants, including 30.0-48.3% increases in freezing tolerance and decreases in LT50 values of approximately 0.7-3.4°C. Thus, the AtICE1 methylation-regulated transcription of CBF pathway genes is responsible for the phenotypic variation in the freezing tolerance observed in A. thaliana.

[Genetic diagnosis of a patient with long-time misdiagnosis of epilepsy].

OBJECTIVE: To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy. METHODS: Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents. CONCLUSION: The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.

Cortisol is associated with low frequency of interleukin 10-producing B cells in patients with atherosclerosis.

It is accepted that inflammation plays a critical role in the development of atherosclerosis; the pathogenesis is not clear. B-cell-produced interleukin (IL) 10 is an immune regulatory cytokine that can inhibit immune inflammation. This study tests a hypothesis that a psychological stress hormone, cortisol, suppresses IL-10 expression in peripheral B cells of patients with atherosclerosis. Peripheral blood samples were collected from patients with coronary artery atherosclerosis. B cells were isolated from the blood samples to be analyzed for the expression of IL-10 and micro RNA (miR) 98 by real-time polymerase chain reaction. We observed that the frequency of IL-10+ B cell was less in patients with atherosclerosis than healthy controls. The serum cortisol levels were higher in the patients than that in healthy controls. Peripheral B-cell frequency was negatively correlated with the serum cortisol levels. Exposure of B cells to cortisol increased the expression of miR-98 in B cells. Cortisol also inhibited the expression of IL-10 in B cells, in which miR-98 played a critical role. Treating B cells from atherosclerosis patients with anti-miR-98 liposomes reversed the ability of expression of IL-10 in the cells. The expression of IL-10 is suppressed in peripheral B cells, which can be up regulated by anti-miR-98 liposomes.

[Analysis of SLC39A4 gene mutation in a patient with acrodermatitis enteropathica].

OBJECTIVE: To detect pathogenic mutation of the SLC39A4 gene in a male patient with acrodermatitis enteropathica (AE). METHODS: Peripheral venous blood sample and clinical data from the patient and his parents were collected. One hundred unrelated healthy individuals were recruited as controls. All coding exons and flanking exon-intron sequences of the SLC39A4 gene were analyzed by PCR and direct sequencing. RESULTS: The results revealed that the patient and his mother have both carried a novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) in exon 6. A novel nonsense mutation c.958C to T (p.Q320X) in exon 5 was also detected in the patient and his father and grandmother. This novel mutation was not detected in the unaffected family members and 100 unrelated healthy controls. CONCLUSION: The novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) derived from the mother and nonsense mutation c.958C to T (p.Q320X) of the SLC39A4 gene derived from the father may underlie the disease in the patient.

[Analysis of TSC gene mutations in five patients with tuberous sclerosis complex].

OBJECTIVE: To identify pathogenic mutations of TSC1 and TSC2 genes in two familial and one sporadic cases with tuberous sclerosis complex (TSC). METHODS: For five patients and their family members, potential mutations of the TSC1 and TSC2 genes were detected by direct sequencing. RESULTS: For one family, a novel missense mutation c.1964C>T (p.S655F) was detected in the exon 19 of the TSC2 gene. For the sporadic patient, a repeat substitution with deletion mutation c.5238-5255delCATCAAGCGGCTCCGCCA (p.His1746GlnfsX56) was detected in the exon 40 of the TSC2 gene, which led to a stop codon TGA after the 56th amino acids. No mutation was found in another family. CONCLUSION: The missense mutation c.1964C>T(P.S655F) and the substitution with deletion mutation 5238-5255delCATCAAGCGGCTCCGCCA(p.His1746GlnfsX56) of the TSC2 gene probably underlie the disease in the first family and the sporadic case.

[Two novel mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria].

OBJECTIVE: To identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria(DSH). METHODS: Clinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing. RESULTS: A novel frame-shift mutation c.2638delG (p.Asp880ThrfsX15) from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c.2867C>A (p.Ser956X) was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls. CONCLUSION: The frame-shift mutation c.2638delG (p.Asp880ThrfsX15) and the nonsense mutation c.2867C>A (p.Ser956X) in the ADAR1 gene probably underlie the DSH in our patients.

[Analysis of TSC gene mutation in a patient with tuberous sclerosis].

OBJECTIVE: To identify pathogenic mutation of the TSC1 and TSC2 genes in a patient with tuberous sclerosis. METHODS: Peripheral venous blood samples and clinical data of a pregnant woman with tuberous sclerosis and 4 family members (parents, uncle and husband) were collected. Genomic DNA was extracted. All coding exons of the TSC1 and TSC2 genes and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing. RESULTS: The patient has presented facial angiofibroma and prefrons fibrous plaque for 20 years, and lumbar connective tissue nevus for 10 years. She also had mental retardation but no epilepsy. A novel frame-shift mutation c.4258-4261delTCAG was detected in exon 34 of the TSC2 gene, which had led to a premature stop codon TAG after the 55th amino acids. The same mutation was not found in the unaffected family members and 100 unrelated healthy controls. CONCLUSION: The novel frame-shifting mutation c.4258-4261delTCAG (p.Ser1420GlyfsX55) in the TSC2 gene may be responsible for the disease in the patient.

Identification of novel KRT5 gene variants in two Chinese patients with sporadic form of epidermolysis bullosa simplex: A case report.

Epidermolysis bullosa simplex (EBS), a rare genetic disorder characterized by fragile skin that is prone to blistering and tearing, is primarily caused by mutations in genes encoding keratin proteins, such as KRT5 and KRT14. This study aimed to identify the pathogenic gene variants responsible for the sporadic form of EBS in two Chinese patients. Blood samples were collected from patients and their parents, and next-generation sequencing (NGS) was performed for variant screening. Two novel gene variants were identified within the KRT5 gene: c.1399A>T (p.Ile467Phe) in patient 1 and c.1412G>A (p.Arg471His) in patient 2. These variants were absent in the unaffected parents and a control group of 100 healthy individuals. These two novel gene variants within the KRT5 gene may be responsible for EBS, thus improving understanding of the genetic basis of EBS.

Identification of a novel nonsense ATP2A2 gene variant in a patient with Darier's disease flare following COVID-19 infection: A case report.

RATIONALE: Darier disease (DD) is a rare autosomal dominant disorder that primarily manifests as hyperkeratotic papules and itching. The underlying etiology of DD is pathogenic variation in the ATP2A2 gene. However, this disease has a high penetrance but variable expressivity, indicating that patients inheriting the genotype may have different manifestations due to exogenous factors. Meanwhile, a few reports have documented that COVID-19 may be implicated in the flare of DD. PATIENT CONCERNS: A 51-year-old man presented with keratotic papules and scaly erythematous rash on his trunk with pruritus after being infected with COVID-19. Laboratory test results were normal. Histological analysis revealed epidermal hyperkeratosis and intraepidermal lacunae containing dyskeratinized cells. Genetic analysis revealed a novel variant of ATP2A2 (c.815G>A, p.Trp272*), which was considered pathogenic in this case. DIAGNOSES: The patient was diagnosed as having DD. INTERVENTIONS: Oral acitretin and topical corticosteroid hormone ointments were used. OUTCOMES: The patient achieved complete resolution of symptoms during the 3-month follow-up period. LESSONS: We revealed the first novel ATP2A2 variant (c.815G>A, p.Trp272*) in the flare of DD following COVID-19 infection. Additionally, this pathogenic variant enriches the ATP2A2 gene mutation spectrum.

Identification of a novel TSC1 gene variant in a patient with atypical vitiligo-like skin lesions: Unveiling the hidden tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC), an autosomal-dominant disorder, is characterized by hamartomas affecting multiple organ systems. The underlying etiology of TSC is the pathogenic variations of the TSC1 or TSC2 genes. The phenotype variability of TSC could lead to missed diagnosis; therefore, the latest molecular diagnostic criteria for identifying a heterozygous pathogenic variant in either the TSC1 or TSC2 gene filled this gap. Furthermore, the pathogenicity of numerous variants remains unverified, potentially leading to misinterpretations of their functional consequences. METHODS: In this study, a single patient presenting with atypical vitiligo-like skin lesions suspected to have TSC was enrolled. Targeted next-generation sequencing and Sanger sequencing were employed to identify a pathogenic variant. Additionally, a minigene splicing assay was conducted to assess the impact of TSC1 c.1030-2A>T, located in intron 10, on RNA splicing. RESULTS: A novel TSC1: c.1030-2A>T heterozygosis variant was identified in intron 10. In vitro minigene assay revealed that the c.1030-2A>T variant caused exon 11 skipping, resulting in a frameshift in the absence of 112 base pairs of mature messenger RNA and premature termination after 174 base pairs (p.Ala344Glnfs*59). CONCLUSION: The detection of this novel pathogenic TSC1 variant in the patient with atypical vitiligo-like skin lesions enrolled in our study ultimately resulted in the diagnosis of TSC. As a result, our study contributes to expanding the mutational spectrum of the TSC1 gene and refining the genotype-phenotype map of TSC.

Effects of a Tai Chi rehabilitation program implemented using a hybrid online and offline mode on oxidative stress and inflammatory responses in patients with coronary heart disease: a randomized controlled trial.

Background: Coronary heart disease (CHD) is the leading cause of death in both developed and many developing countries. Exercise training is a fundamental component of cardiac rehabilitation programs for patients with CHD. This study aims to investigate the effects of a Tai Chi rehabilitation program, which is provided through a hybrid online and offline mode, on oxidative stress and inflammatory responses in patients with CHD. Methods: A total of 34 patients with coronary heart disease were randomly assigned to two groups: an experiment group (n = 14, age 62.07 ± 9.076 years) and a control group (n = 20, age 61.90 ± 9.700 years). The experiment group underwent a 12-week Tai Chi cardiac rehabilitation program (TCCRP), while the control group followed a conventional exercise rehabilitation program (CERP) consisting of 1-h sessions, 3 times per week, for a total of 36 sessions. Participants were studied at baseline and post-intervention. The main assessments include the levels of Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor (TNF-α) and Interleukin-10 (IL - 10) in blood samples. Pearson correlation analysis was used, and the differences between the two groups were subsequently tested using two-way repeated ANOVA. Statistical significance was defined as a two-sided p-value of <0.05. Results: The key finding of the study reveals that MDA was significantly reduced by 1.027 nmoL/mL. Additionally, the TCCRP showed significant improvements in SOD and IL-10, with values of 10.110 U/mL and 2.441 pg./mL, respectively. Notably, a significant positive correlation was found between SOD and IL-10 (r = 0.689, p = 0.006), while MDA showed a significant positive correlation with TNF-a (r = 0.542, p = 0.045). In contrast, the ECRP group only showed a significant improvement in SOD. Conclusion: The study conducted a 12-week program on TCCRP, which utilized a hybrid online and offline model for individuals with coronary heart disease. The program showed promising results in alleviating oxidative stress and inflammation, possibly by regulating the balance between oxidative and antioxidative factors, as well as pro-inflammatory and anti-inflammatory factors.

Effectiveness of an online/offline mixed-mode Tai Chi cardiac rehabilitation program on microcirculation in patients with coronary artery disease: A randomized controlled study.

OBJECTIVE: We explored the effectiveness of an online/offline mixed-mode Tai Chi cardiac rehabilitation program on the microcirculation of patients with coronary artery disease (CAD). DESIGN: Prospective, randomized controlled study. SETTING: It was conducted in a tertiary hospital. SUBJECTS: Twenty-six patients who met the diagnostic criteria for coronary artery disease were recruited. INTERVENTIONS: Patients were randomized divided into a 12-week Tai Chi cardiac rehabilitation program(TCCRP) or a conventional exercise rehabilitation program(CERP) in a 1:1 fashion, 4 weeks of in-hospital rehabilitation and 8 weeks of online rehabilitation at home (a total of 12 weeks of intervention). MAIN OUTCOME MEASURES: Nailfold microcirculation (Morphological integrals, Blood flow integrals, Periphery capillary loop integrals, Overall integrals). MAIN OUTCOME MEASURES: Twenty patients completed the study. The Morphological integrals (baseline: 2.875±1.171 vs 12weeks: 1.863±0.414, t = 2.432, P = 0.045 < 0.05) and Overall integrals (baseline: 5.563±2.001 vs 12weeks: 3.688±1.167, t = 3.358, P = 0.012 < 0.05) decreased significantly in the TCCRP, The nailfold microcirculation integra decreased not significantly in the CERP (P > 0.05). The nailfold microcirculation integra was not significantly different between the two groups after the intervention (P > 0.05). CONCLUSIONS: The TCCRP improved the microcirculation of patients with CAD.

Individualized quantified tricuspid valve annuloplasty for treating Ebstein anomaly.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate whether individualized quantified selective tricuspid valve annuloplasty would be suitable for the treatment of Ebstein anomaly. METHODS: Between March 1999 and February 2011, a total of 23 patients with Ebstein anomaly underwent individualized quantified selective tricuspid valve annuloplasty at the authors' institution. The annulus was reconstructed according to each patient's individual anatomic characteristics of their tricuspid valve. Echocardiography was used to assess the changes of tricuspid valve regurgitation and heart function perioperatively and also during the follow up period. RESULTS: There was no hospital mortality. One patient died suddenly at 41 months after surgery, and two patients were lost to follow up; the remaining patients are still alive. During the follow up, tricuspid valve regurgitation and cardiac function were improved in all patients postoperatively, with no acquired tricuspid stenosis. CONCLUSION: The study results and analysis of follow up data suggested that an '...individualized quantified selective concept and technique of tricuspid valve reconstruction' is reasonable, suitable, and practical in the treatment of Ebstein anomaly.

Levosimendan improves postoperative heart function recovery and prognosis in patients with heart disease.

BACKGROUND: Previous studies have shown that levosimendan can reduce mortality and complications in patients undergoing cardiac surgery. The purpose of this study was to investigate the effect of levosimendan on the recovery of cardiac function, quality of life and prognosis in patients with heart disease after operation. METHODS: From October 2017 to August 2019, 93 patients admitted to our hospital for cardiac surgery were retrospectively enrolled in this study. Fifty-three patients treated with levosimendan were included in the experimental group (EG) and 40 who did not receive levosimendan were recruited into the control group (CG). After operation, the length of ICU stay and hospitalization, mean arterial pressure, central venous pressure, heart rate, the changes of cardiac parameters (left ventricular end diastolic volume (LVEDV), end-systolic volume (LVESV), left ventricular ejection index (LVEF) and cardiac index (CI) at different time points), and the changes of high sensitive troponin I (hs-cTnI), creatine kinase isoenzyme (CK-MB) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were compared between the two groups. The stroke volume index (SVI), left ventricular stroke work index (LVSWI), systemic vascular resistance index (SVRI) and other hemodynamic indexes were also compared. RESULTS: The length of ICU stay and hospitalization time in the EG were shorter than those in the CG. After treatment, MAP (mean arterial pressure), CVP (central venous pressure), HR (heart rate), LVEDV, LVESV, HS CTN, NT proBNP and SVRI in the EG were lower than those in the CG group, while LVEF, CI, SVI and LVSWI were higher than those in the CG. The quality of life of patients in the EG was better than that of those in the CG one month after treatment. Logistics regression analysis revealed that the use of levosimendan can reduce the risk of death. CONCLUSION: Levosimendan can improve the cardiac function and prognosis of patients after cardiac surgery, which is worthy of clinical promotion.

Identification of a novel heterozygous TSC2 splicing variant in a patient with Tuberous sclerosis complex: A case report.

RATIONALE: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by facial angiofibromas, epilepsy, intellectual disability, and the development of hamartomas in several organs, including the heart, kidneys, brain, and lungs. Mutations in either TSC1 or TSC2 result in dysregulated mTOR activation, leading to the occurrence of TSC. PATIENT CONCERNS: A 44-year-old man was hospitalized for acute lumbago and hematuria. DIAGNOSIS: The patient presented with facial angiofibromas, epilepsy, fibrous plaques, periungual fibroma, renal angiomyolipomas (AML), pulmonary lymphangioleiomyomatosis (LAM), liver hamartomas, and osteosclerosis. A diagnosis of TSC was made based on clinical manifestations. INTERVENTIONS: Next-generation sequencing (NGS) was performed to screen for potential variants, which were verified using Sanger sequencing. The final variant was analyzed using a minigene assay. OUTCOMES: A potentially pathogenic novel TSC2 variant (NM_000548.4, c.336_336 + 15delGGTAAGGCCCAGGGCG) was identified using NGS and confirmed using Sanger sequencing. The in vitro minigene assay showed that the variant c.336_336 + 15delGGTAAGGCCCAGGGCG caused erroneous integration of a 74 bp sequence into intron 4. This novel variant was not found in his unaffected parents or 100 unrelated healthy controls. LESSONS: We identified a novel heterozygous TSC2 variant, c.336_336 + 15delGGTAAGGCCCAGGGCG, in a patient with classical TSC and demonstrated that this variant leads to aberrant splicing using a minigene assay. Our results extend the understanding of the mutational spectrum of TSC2.

Voxel-wise Functional Connectivity of the Default Mode Network in Epilepsies: A Systematic Review and Meta-Analysis.

BACKGROUND: Default Mode Network (DMN) is recognized to be involved in the generation and propagation of epileptic activities in various epilepsies. Converging evidence has suggested disturbed Functional Connectivity (FC) in epilepsies, which was inferred to be related to underlying pathological mechanisms. However, abnormal changes of FC in DMN revealed by different studies are controversial, which obscures the role of DMN in distinct epilepsies. OBJECTIVE: The present work aims to investigate the voxel-wise FC in DMN across epilepsies Methods: A systematic review was conducted on 22 published articles before October 2020, indexed in PubMed and Web of Science. A meta-analysis with a random-effect model was performed using the effect-size signed differential mapping approach. Subgroup analyses were performed in three groups: Idiopathic Generalized Epilepsy (IGE), mixed Temporal Lobe Epilepsy (TLE), and mixed Focal Epilepsy (FE) with different foci. RESULTS: The meta-analysis suggested commonly decreased FC in mesial prefrontal cortices across different epilepsies. Additionally decreased FC in posterior DMN was observed in IGE. The TLE showed decreased FC in temporal lobe regions and increased FC in the dorsal posterior cingulate cortex. Interestingly, an opposite finding in the ventral and dorsal middle frontal gyrus was observed in TLE. The FE demonstrated increased FC in the cuneus. CONCLUSION: The current findings revealed both common and specific alterations of FC in DMN across different epilepsies, highlighting the contribution of these dysfunctions to epileptic activities and cognitive behaviors in patients. Furthermore, the current study provided powerful evidence to support DMN as a potential candidate for effective intervention in epilepsy.