Novel heterozygous mutation of CACNA2D1 gene in a Chinese family with arrhythmia.

BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

Salicylic Acid Treatment Ameliorates Postharvest Quality Deterioration in 'France' Prune (Prunus domestica L. 'Ximei') Fruit by Modulating the Antioxidant System.

The potential of salicylic acid (SA) in delaying postharvest fruit senescence has been extensively documented; nevertheless, its effect on antioxidant activity and quality of 'France' prune fruit is largely unknown. The study investigated the effects of SA (0.5 mM) on postharvest quality deterioration of 'France' prune fruit. Results indicated that SA impeded the increase in respiration rate and weight loss, and mitigated the decrease of soluble solids content (SSC), titratable acidity (TA) content, firmness, and hue angle. SA sustained the ascorbate-glutathione cycle by inducing the production of ascorbic acid (AsA) and glutathione (GSH) and attenuates flavonoids, total phenols, and anthocyanins degradation by inhibiting polyphenol oxidase (PPO) activity and PdPPO. Moreover, SA significantly improved superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD), and glutathione reductase (GR) activities and gene expression levels, sustained higher 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging capacity, ferric reducing antioxidant power (FRAP), and hydroxyl radical (·OH) inhibition capacity, and impeded the production of hydrogen peroxide (H2O2) and superoxide anion (O2•-). Overall, SA improved the antioxidant capacity by inducing the synthesis of defense response-related substances and promoting antioxidant enzyme activities to sustain the storage quality of 'France' prune fruit.

Batch Preparation and Performance Study of Boehmite-Based Electrospun Nanofiber Separators for Lithium-Ion Batteries.

The design and preparation of high-performance separators for lithium-ion batteries (LIBs) have far-reaching practical significance in enhancing the overall performance of LIBs. Electrospun nanofiber separators (ENSs) have the characteristics of large specific surface area, high porosity, small pore size and good affinity with the electrolyte, making them become ideal candidates for LIB separators. In this work, polyacrylonitrile (PAN)/polyurethane (PU) (PAU) ENSs loaded with boehmite (BM) particles (BM/PAU ENSs) were mass-produced using spherical section free surface electrospinning (SSFSE), and used as LIB separators. Their morphology, structures and performances were tested and characterized. The results showed that all BM/PAU ENSs maintained excellent thermal dimensional stability in the range of 140-180 °C, and had good electrolyte wettability and high porosity. The composite BM/PAU-2 ENS with the best performance had a porosity of 52.5%, an electrolyte uptake rate of 822.1%, and an ionic conductivity of 1.97 mS/cm. Additionally, the battery assembled with BM/PAU-2 separator also demonstrated best electrochemical performance, cycling performance, and rate capability, with a capacity retention rate of 94.4% after 80 cycles at 0.5 C, making it a promising high-performance separator for LIBs.

Association between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine.

BACKGROUND: The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. METHODS: This study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. RESULTS: The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. CONCLUSIONS: This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.

Comparison of different drying pretreatment combined with ultrasonic-assisted enzymolysis extraction of anthocyanins from Lycium ruthenicum Murr.

Extraction of anthocyanins from Lycium ruthenicum Murr. (L. ruthenicum) is a notable challenge in food production, requiring methods that balance efficiency and safety. In this study, we conducted a comparative analysis the extraction of anthocyanins by natural air drying (NAD), vacuum freeze drying (VFD), hot air drying (HAD), and vacuum microwave drying (MVD) combined with ultrasonic-assisted enzymolysis extraction (UAEE). The results demonstrated that the extraction yield and antioxidant activity of anthocyanins were significantly higher in VFD. This phenomenon can be attributed to the modification of raw material's microstructure, leading to an increased extraction yield of specific anthocyanins such as Cyanidin-3-galactoside, Delphinidin chloride, Cyanidin, and Petunidin. According to the pretreatment results, the extraction process of anthocyanins was further optimized. The highest yield (3.16 g/100 g) was obtained in following conditions: 0.24 % pectinase, 48 °C, solid:liquid = 1:21, and 21 min ultrasonic time. This study improves the commercial value and potential application of L. ruthenicum in food industry.

Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.

Profiles of HBcrAg and pgRNA in Pregnant Women With Chronic HBV Under Different Disease Phases and Antiviral Prophylaxis.

Background: Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal-infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB. Methods: This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum. Results: The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)-positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0-5.9] vs 8.6 [8.4-8.7] log10 U/mL; P < .01) and pgRNA (median [IQR], 0.0 [0.0-2.5] vs 7.8 [7.6-8.1] log10 copies/mL; P < .01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P < .05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 (P < .05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively (P > .05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg. Conclusions: HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients.

Identification of a de novo CACNA1B variant and a start-loss ADRA2B variant in paroxysmal kinesigenic dyskinesia.

Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary movements triggered by a sudden voluntary action. In this study, whole-exome sequencing was conducted on a cohort of Chinese patients to identify causal mutations. In one young female case, a de novo CACNA1B variant (NM_000718.3:exon3:c.479C > T:p.S160F) was identified as the causative lesion. This finding may broaden the phenotypic spectrum of CACNA1B mutations and provide a prospective cause of primary PKD. Additionally, a novel start-loss variant (NM_000682.7:c.3G > A) within ADRA2B further denied its association with benign adult familial myoclonic epilepsy, and a KCNQ2 E515D variant that was reported as a genetic susceptibility factor for seizures had no damaging effect in this family. In sum, this study established a correlation between CACNA1B and primary PKD, and found valid evidence that further negates the pathogenic role of ADRA2B in benign adult familial myoclonic epilepsy.

Effects of variable-temperature drying on the qualities and sweet-substance profile of Zizyphus jujuba Mill. cv. Junzao.

The changes in the qualities and sweet-substance levels of Junzao jujube during variable-temperature drying (VTD) were investigated. The results showed that VTD retains the original color of jujube, reduces its hardness and chewiness, and decreases its wrinkling while shortening the drying time by 13.2% compared with that of constant temperature drying (CTD). "Electronic-tongue" taste analysis showed that the sweetness of VTD jujube is significantly higher than that for CTD. This is shown to be related to the contents of sucrose, fructose, and glucose, as well as the activities of invertase and sucrose synthase enzymes. In addition, the content trends for sweet amino acids are correlated with the temperature gradient used in VTD. Thus, the present study elucidates the factors governing the transformation of sugar substances in jujube during VTD, as well as providing a practical reference for the application of VTD in the jujube industry.

Effects of ultrasonication and freeze-thaw pretreatments on the vacuum freeze-drying process and quality characteristics of apricot (Prunus armeniaca L. cv. Diaoganxing).

The combination of pretreatment and vacuum freeze-drying (VFD) technology is an effective technique for extending the shelf life of apricots, reducing costs and energy consumption. However, the impact of pretreatment on the freeze-drying and quality characteristics of apricots is still unclear. The effects of ultrasound (US), freeze-thaw (FT), and their combination (FT-US) on water migration and quality characteristics of apricot slices on VFD were studied. LR-NMR and SEM showed that pretreatment significantly reduced the time (19.05%-33.33%) and energy consumption (17.67%-35.66%) of the VFD process. Compared with the control group, the US, FT, and FT-US improved the color, texture, rehydration ability, and flavor of apricot slices. Among them, FT-US retained the most biologically active substances and antioxidant capacity, with the highest sensory score. Overall, FT-US pretreatment induced changes in the microstructure and chemistry of apricots, which contributed to the production of high-quality VFD apricot slices.

Characterization of macrophages in ischemia-reperfusion injury-induced acute kidney injury based on single-cell RNA-Seq and bulk RNA-Seq analysis.

Acute kidney injury (AKI) is a complex disease, with macrophages playing a vital role in its progression. However, the mechanism of macrophage function remains unclear and strategies targeting macrophages in AKI are controversial. To address this issue, we used single-cell RNA-seq analysis to identify macrophage sub-types involved in ischemia-reperfusion-induced AKI, and then screened for associated hub genes using intersecting bulk RNA-seq data. The single-cell and bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially-expressed genes (DEGs) and pseudo-bulk DEG analyses were used to identify common hub genes. Pseudotime and trajectory analyses were performed to investigate the progression of cell differentiation. CellChat analysis was performed to reveal the crosstalk between cell clusters. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify enriched pathways in the cell clusters. Immunofluorescence and RT-PCR were preformed to validate the expression of the identified hub genes. Four hub genes, Vim, S100a6, Ier3, and Ccr1, were identified in the infiltrated macrophages between normal samples and those 3 days after ischemia-reperfusion renal injury (IRI); all were associated with the progression of IRI-induced AKI. Increased expression of Vim, S100a6, Ier3, and Ccr1 in infiltrated macrophages may be associated with inflammatory responses and may mediate crosstalk between macrophages and renal tubular epithelial cells under IRI conditions. Our results reveal that Ier3 may be critical in AKI, and that Vim, S100a6, Ier3, and Ccr1 may act as novel biomarkers and potential therapeutic targets for IRI-induced AKI.

Identification and prognostic analysis of candidate biomarkers for lung metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.

Correction to: Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway.

[This corrects the article DOI: 10.1002/mco2.226.].

RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability.

Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.

Primary hepatic mucosa-associated lymphoid tissue lymphoma complicated with atrial fibrillation: A case report and literature review.

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignant primary hepatic lymphoma. The sensible choice of treatment for patients with primary lymphoma combined with atrial fibrillation (AF) is controversial and challenging. PATIENT CONCERNS: The patient presented with both primary hepatic MALT lymphoma and AF, which was difficult to manage. DIAGNOSES: Pathological and immunohistochemical examination are helpful for definitive diagnosis. INTERVENTIONS: Surgical resection and subsequent anticoagulant therapy are main treatment methods, and adjuvant therapy depends on the situation. OUTCOMES: Primary hepatic MALT lymphoma is easy to misdiagnosis due to a lack of typical symptoms and imaging signs. LESSONS: This case highlights for patients with primary hepatic MALT lymphoma combined with AF, toxicity caused by adjuvant chemotherapy should be fully considered, and careful selection should be made based on the general conditions and complications of patients.

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1.

Lipin proteins including Lipin 1-3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

Bi-directional nasal drug delivery systems: A scoping review of nasal particle deposition patterns and clinical application.

Objectives: To compare the deposition patterns within the nasal cavity between the bi-directional and unilateral nasal delivery systems. And to summarize the clinical application of the bi-directional nasal drug delivery devices. Data source: PubMed, Cochrane Library, Embase, and Web of Science databases. Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We included studies exploring patterns and influencing factors of particle depositions within the nasal cavity among patients, healthy controls, and nose cast models using the bi-directional and unilateral nasal delivery system. The clinical application of the bi-directional delivery devices was also summarized. Results: A total of 24 studies were included in this review. Bi-directional nasal delivery systems utilize forced exhalation to power the delivery of drugs to deeper areas of the nasal cavity and paranasal sinuses. Unilateral nasal delivery systems included traditional liquid spray pumps, the aerosol mask system, nebulization, and conventional nasal inhalation. Compared with unilateral delivery systems, the bi-directional nasal delivery system provided a more extensive and efficient nasal deposition in the nasal cavity, especially in the olfactory cleft, without lung deposition. Several parameters, including particle size, pulsatile flow, and nasal geometry, could significantly influence nasal deposition. The bi-directional nasal delivery system enables better delivery of steroids or sumatriptan to the sinonasal cavity's high and deep target sites. This bi-directional delivery device demonstrated an effective and well-tolerated treatment that produced high drug utilization, rapid absorption, and sustained symptom improvement among patients with chronic rhinosinusitis (CRS) or migraine. Conclusion: The bi-directional nasal drug delivery systems demonstrated significantly higher drug deposition in superior and posterior regions of the nasal cavity than unilateral nasal delivery systems. Further studies should explore its potential role in delivering drugs to the olfactory cleft among patients with olfactory disorders and central nervous system diseases. Level of evidence: N/A.

Laparoscopic pancreaticoduodenectomy versus open pancreaticoduodenectomy for carcinoma of the ampulla of Vater in a medium-volume center: a propensity score matching analysis.

OBJECTIVE: To compare the efficacy of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in a medium-volume medical center. METHODS: Data for patients who underwent OPD or LPD for carcinoma of the ampulla of Vater (VPC) between January 2017 and June 2022 were acquired retrospectively. Propensity score-matching (PSM) analysis was performed to balance the baseline characteristics between the groups. The primary outcome was disease-free survival (DFS). Cox regression analysis was used to explore the independent risk factors for DFS. RESULTS: A total of 124 patients with pathologically diagnosed VPC were included. After 1:1 matching, there were 23 cases each in the OPD and LPD groups. Kaplan-Meier survival analyses showed that the median DFS in the OPD and LPD groups was identical (16.0 months vs 16.0 months, respectively). Multivariate Cox regression analysis showed that low levels of alkaline phosphatase and γ-glutamyl transpeptidase, positive surgical margin, and lymph node enlargement were independent risk factors for DFS. CONCLUSION: LPD in medium-volume centers with acceptable technical conditions may approach or even achieve the efficacy of LPD in large-volume centers.

Is endoscopic radiofrequency ablation plus stent placement superior to stent placement alone for the treatment of malignant biliary obstruction? A systematic review and meta-analysis.

OBJECTIVE: Malignant biliary obstruction (MBO) is a rare disease with a poor prognosis. Recent studies have shown that endoscopic radiofrequency ablation (ERFA) may improve survival. We conducted a systematic review and meta-analysis of the efficacy of ERFA in combination with biliary stent placement for the treatment of MBO. METHODS: The study was registered in INPLASY (number 202340096). The PubMed, Cochrane Library, Web of Science, and Embase databases were searched from inception to April 2023. We selected studies comparing the efficacy of ERFA plus stent placement with stent placement alone. The primary outcomes were pooled hazard ratios (HRs) for overall survival and stent patency; the secondary outcomes were the odds ratios (ORs) for adverse events. RESULTS: Eleven studies (four randomized controlled trials and seven observational studies) were included in the meta-analysis. Pooled analysis showed a difference in survival time between the two groups (HR 0.65, 95% confidence interval [CI] 0.58-0.73, I2 = 40%). However, there were no differences in the duration of stent patency or the incidence of adverse events (HR 1.04, 95% CI 0.84-1.29, I2 = 46%; OR 1.41, 95% CI 1.02-1.96, I2 = 29%). CONCLUSIONS: ERFA has a significant survival benefit for MBO, but does not increase the risk of adverse events.

Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient.

Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear. Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family. Results: A novel splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant. Conclusion: A novel heterozygous splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.