Pedigree Analysis of Nonclassical Cholesteryl Ester Storage Disease with Dominant Inheritance in a LIPA I378T Heterozygous Carrier.

BACKGROUND: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. METHODS: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. RESULTS: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. CONCLUSIONS: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation.

Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Adult type I Gaucher disease with splenectomy caused by a compound heterozygous GBA1 mutation in a Chinese patient: a case report.

Gaucher disease (GD) is an autosomal recessive ailment resulting from glucocerebrosidase deficiency caused by a mutation in the GBA1 gene, leading to multi-organ problems in the liver, spleen, and bone marrow. In China, GD is extremely uncommon and has a lower incidence rate than worldwide. In this study, we report the case of an adult male with an enlarged spleen for 13 years who presented with abdominal distension, severe loss of appetite and weight, reduction of the three-line due to hypersplenism, frequent nosebleeds, and bloody stools. Regrettably, the unexpected discovery of splenic pathology suggestive of splenic Gaucher disease was only made after a splenectomy due to a lack of knowledge about rare disorders. Our patient's delayed diagnosis may have been due to the department where he was originally treated, but it highlights the need for multidisciplinary consultation in splenomegaly of unknown etiology. We then investigated the patient's clinical phenotypes and gene mutation features using genetically phenotypical analysis. The analysis of the GBA1 gene sequence indicated that the patient carried a compound heterozygous mutation consisting of two potentially disease-causing mutations: c.907C > A (p. Leu303Ile) and c.1448 T > C (p. Leu483Pro). While previous research has linked the p. Leu483Pro mutation site to neurologic GD phenotypes (GD2 and GD3), the patients in this investigation were identified as having non-neuronopathic GD1. The other mutation, p. Leu303Ile, is a new GD-related mutation not indexed in PubMed that enriches the GBA1 gene mutation spectrum. Biosignature analysis has shown that both mutations alter the protein's three-dimensional structure, which may be a pathogenic mechanism for GD1 in this patient.

A correlation study between prostate necrosis rate calculated by 3D Slicer software and clinical efficacy of prostatic artery embolization, along with an analysis of predictors of clinical success after prostatic artery embolization.

PURPOSE: To analyze the correlation between the prostate necrosis rate at 1-month after prostatic artery embolization (PAE) and the clinical efficacy at 1-year after PAE, and to explore potential predictors of clinical success after PAE for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). METHODS: The prostate magnetic resonance imaging data at 1-month after PAE were imported into 3D Slicer software for calculating the prostate necrosis rate and thus analyzing the relationship between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after PAE. The 151 patients with PAE technical success were divided into a clinical success group (n = 126) and a clinical failure group (n = 25). Independent predictors of clinical success after PAE were analyzed by multifactorial logistic regression, and the predictive performance of each factor was evaluated by applying the receiver operating characteristic curve and the area under the curve (AUC). RESULTS: There was a linear negative correlation between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after surgery (P < 0.001). In the clinical success group, both the initial prostate volume (PV) and the prostate necrosis rate at 1-month after PAE were significantly higher than in the clinical failure group (P < 0.001), and acute urinary retention (AUR) and adenomatous-dominant BPH were also associated with clinical success (P < 0.05). Multifactorial logistic regression analysis revealed that larger initial PV, a higher prostate necrosis rate at 1-month after surgery, and AUR were independent predictors of clinical success after PAE. The AUC values for these three indicators and their combination were 0.720, 0.928, 0.599, and 0.951, respectively, in which the prostate necrosis rate at 1-month after PAE demonstrating a high predictive value. CONCLUSION: The higher the prostate necrosis rate at 1-month after PAE, the better the clinical efficacy at 1-year after PAE is likely to be, and the prostate necrosis rate at 1-month after PAE is expected to become a predictor of clinical success after PAE.

Potential regulatory role of the Nrf2/HMGB1/TLR4/NF-κB signaling pathway in lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+ plasma cells subset (PCs) in LN. METHODS: C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin-eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+ PC subsets in the blood and kidneys of mice were determined by flow cytometry. RESULTS: In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1ß and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression. CONCLUSION: This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.

Pharmarcomechanical thrombectomy combined with transluminal balloon angioplasty for treating transplant renal vein thrombosis.

Renal vein thrombosis (RVT) is a rare vascular complication that occurs after renal transplantation and usually results in irreversible kidney damage and graft loss. We report the case of a patient who underwent right iliac fossa allogeneic kidney transplantation and developed RVT combined with ipsilateral thrombosis from the popliteal to the femoral veins, with extension to the common iliac veins, 4 months after transplantation. Under unfractionated heparin anticoagulation, an Aegisy (Life Tech Scientific Co., Ltd., Shenzhen, China) vena cava filter was placed to prevent pulmonary embolism. Percutaneous mechanical thrombectomy combined with balloon angioplasty was performed to aspirate the thrombus and successfully dilate the narrow venous lumen. The patient's renal function was restored postoperatively. Ultrasonography showed the allograft and ipsilateral lower extremity deep veins to be fluent and patent. To conclude, in patients with RVT after renal transplantation, percutaneous mechanical thrombectomy in conjunction with balloon angioplasty can be performed with desirable outcomes and no severe adverse effects. This method reduces the risk of bleeding from exposure to systemic intravenous thrombolysis and avoids surgery-associated trauma.

Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt-Hogg-Dubé syndrome.

To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt-Hogg-Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fumarate hydratase (FH)-deficient papillary RCC via pathological biopsy carried two heterozygous variants: FH (NM_000143.3) missense mutation c.1189G>A (p.Gly397Arg) and FLCN (NM_144997.5) frameshift mutation c.1579_1580insA (p.Arg527Glnfs*75). No family member carrying a single variant had renal tumours. In HEK293T cells transfected with mutant vectors, mRNA and protein expression after FLCN p.Arg527Glnfs*75 and FH p.Gly397Arg mutations were significantly lower than those in wild-type (WT) cells. Cell immunofluorescence showed altered protein localisation and reduced protein expression after FLCN p.Arg527Glnfs*75 mutation. The FH WT was uniformly distributed in the cytoplasm, whereas FH protein expression was reduced after the p.Gly397Arg mutation and scattered sporadically with altered cell localisation. Patients with two variants may have a significantly increased penetrance of RCC.

Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis.

Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has good efficacy in the treatment of unresectable hepatocellular carcinoma (uHCC), with a relatively high objective response rate (ORR) compared to conventional transarterial chemoembolization (cTACE). This study aimed to evaluate the safety and medium-term clinical efficacy of DEB-TACE combined with lenvatinib (LEN) plus PD-1 inhibitors as a triple therapy for the treatment of uHCC. Methods: Data of patients with uHCC who received triple therapy of DEB-TACE combined with LEN plus PD-1 inhibitors from January 2019 to June 2021 were analyzed retrospectively. The study endpoints were ORR, progression-free survival (PFS), and treatment-related adverse events based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Thirty-five patients were included in this study, with a median follow-up period of 15 months. The median cycle of DEB-TACE was 1, while that of all forms of TACE procedures per patient was 2. The median administration time of LEN was 7 months, and the median number of PD-1 inhibitor treatment was 4 cycles. The ORR based on mRECIST was 82.9%, disease control rate was 91.4%, and the median time to response was 7 weeks. Among these, the ORR of Barcelona Clinic Liver Cancer (BCLC) stage A reached 100%, while that of BCLC stages B and C reached 84.6% and 78.9%, respectively. The median PFS was 9 months; the mOS was not reached. Fourteen patients (40%) successfully underwent downstaging conversion and surgical resection, 32 patients (91.4%) experienced treatment-related adverse events, and no grade 5-related adverse reactions occurred. Conclusion: DEB-TACE combined with LEN and PD-1 inhibitors has a high ORR and surgical conversion rate in the treatment of uHCC tumors, and the toxicity and side effects were tolerable.

Safety and Efficacy of Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma: A Single Center Experience.

Purpose: In China, many patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. Several studies have shown that triple therapy [transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs)] is beneficial for patient survival. In this study, we aimed to evaluate the efficacy of triple therapy (TACE + TKIs + ICIs) for unresectable HCC (uHCC) and the conversion rate of surgical resection (SR). The primary endpoints were objective response rate (ORR) and disease control rate (DCR) based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST v1.1 and adverse events (AEs), while the secondary endpoint was the conversion rate of patients with uHCC treated with triple therapy followed by SR. Patients and Methods: Forty-nine patients with uHCC who received triple therapy at Fujian Provincial Hospital between January 2020 and June 2022 were retrospectively included. The treatment efficacy, SR conversion rate, and associated AEs were recorded. Results: Among the 49 patients enrolled, the ORRs assessed by mRECIST and RECIST v1.1 were 57.1% (24/42) and 14.3% (6/42), respectively, and the DCRs were 92.9% (39/42) and 88.1% (37/42), respectively. Seventeen (34.7%) patients met the criteria for resectable HCC and underwent resection. The median interval between the start of triple therapy and resection was 113.5 days (range 94.75 to 182 d), and the median number of TACE was 2 (range 1 to 2.5). The patients did not achieve median overall survival or median progression-free survival. Treatment-related AEs occurred in 48 (98%) patients, and 18 (36.7%) patients had grade ≥3 AEs. Conclusion: Triple combination therapy resulted in a relatively high ORR and conversion resection rate following uHCC treatment.

Eighteen cases of renal aneurysms: Clinical retrospective analysis and experience of endovascular interventional treatment.

Background: Development of endovascular interventional techniques gradually replaced traditional open surgery and has become the preferred treatment for renal aneurysms. This study aimed to analyze the clinical characteristics of renal artery aneurysm (RAA) and the safety and efficacy of intravascular interventional treatment. Materials and Methods: We retrospectively analyzed the clinical characteristics and imaging data of 23 aneurysms in 18 patients with RAA. The technical success rate, complication rate, mortality rate, reintervention rate, and use of embolization materials were evaluated. Results: In 18 patients with RAA (age, 32-72 years, average age, 52.2 ± 11.2 years), a total of 23 aneurysms were found (diameter 0.5-5.5 cm, average diameter 2.2 ± 1.4 cm). Among them, 11 cases (61.1%) were discovered accidentally, and the remaining patients were diagnosed due to the following major complaints: four cases (22.2%) presented low back pain, two (11.1%) were due to high blood pressure, and one (5.5%) had low back pain with gross hematuria. A total of 14 aneurysms in 13 patients received endovascular interventional therapy. The technical success rate of 13 patients with renal aneurysms was 100%. Three of the 18 patients were lost to follow-up, and the remaining were followed up for 4-89 months. There was no recurrence of the aneurysm or displacement of the stent or coil. Conclusion: Endovascular treatment for RAA has a high success rate, low complication rate, and low reintervention rate. It has the advantage of less trauma and is flexible and more targeted for different types of renal aneurysms.

Han family with essential tremor caused by the P421L variant of the TENM4 gene in China.

BACKGROUND: Essential tremor (ET) is an autosomal dominant inheritance disorder. Mutations in fusion sarcoma (FUS), mitochondrial serine peptidase 2 (HTRA2), teneurin transmembrane protein 4 (TENM4), sortilin1 (SORT1), SCN11A, and notch2N-terminal-like (NOTCH2NLC) genes are associated with familial ET. METHODS: A proband with ET was tested using whole-exome sequencing and repeat-primed polymerase chain reaction. Subsequently, the family members were screened for the suspected mutation, and the results were verified using Sanger sequencing. The relationship between pedigree and phenotype was also analyzed, and structural and functional changes in the variants were predicted using bioinformatics analysis. RESULTS: In a family with ET, the proband (III4) and the proband's father (II1), grandfather (I1), uncle (II2), and cousin (III5) all presented with involuntary tremors of both upper limbs. The responsible mutation was identified as TENM4 c.1262C > T (p.P421L), which showed genetic co-segregation in the family survey. AlphaFold predicted a change in the spatial position of TENM4 after the P421L mutation, which may have affected its stability. AlphaFold also predicted P421L to be a deleterious variation, which would lead to lower degrees of freedom of the TENM4 protein, thereby affecting the protein's structure and stability. According to the bioinformatics analysis, TENM4 (p.P421L) may reduce the signal reaching the nucleus by affecting the expression of TENM4 messenger RNA (mRNA), thereby impairing the normal oligodendrocyte differentiation process and leading to impaired myelination. CONCLUSION: This study revealed that the TENM4 (p.P421L) pathogenic missense variation was responsible for ET in the proband.

Comprehensive analysis of immune ferroptosis gene in renal clear cell carcinoma: prognosis and influence of tumor microenvironment.

OBJECTIVE: We conducted an in-depth study of the immune system and ferroptosis to identify prognostic biomarkers and therapeutic targets for renal clear cell carcinoma. METHODS: Immune ferroptosis-related differentially expressed genes (IFR-DEGs) were selected from The Cancer Genome Atlas (TCGA). A lasso-Cox risk scoring model was established; its prognostic value was determined using prognostic analysis and single multivariate Cox analysis. Model genes were subjected to subcellular fluorescence localization, mRNA and protein expression analyses, and single-cell RNA sequencing localization analysis. Risk score was analyzed using the immune score, immune infiltrating cell correlation, immune checkpoint, TIDE, and drug sensitivity. RESULTS: A total of 103 IFR-DEGs were identified; a risk model comprising ACADSB, CHAC1, LURAP1L, and PLA2G6 was established. The survival curve, single multivariate Cox regression, and receiver operating characteristic (ROC) curve analysis showed that the model had good predictive ability (p < 0.05). It was also validated using the validation set and total cohort. Subcellular fluorescence localization revealed that ACADSB, CHAC1, and PLA2G6 were distributed in the cytoplasm and LURAP1L in the nucleus. The mRNA and protein expression trends were consistent. Single-cell RNA sequencing mapping revealed that ACADSB was enriched in distal tubule cell clusters. In the Kidney renal clear cell carcinoma (KIRC) mutation correlation analysis, 1.56% of the patients were found to have genetic alterations; The Spearman correlation analysis of model gene mutations showed that ACADSB was positively correlated with LURAP1L, which may have a synergistic effect; it was negatively correlated with CHAC1 and PLA2G6, and CHAC1 was negatively correlated with LURAP1L, which may have an antagonistic effect. Model and immune correlation analyses found that high-risk patients had significantly higher levels of CD8+ T cells, regulatory T cells (Tregs), immune checkpoints, immune scores, and immune escape than those in low-risk patients. High-risk patients had a higher susceptibility to small-molecule drugs. CONCLUSION: A novel prognostic model of immune ferroptosis-related genes (ACADSB, CHAC1, LURAP1L, and PLA2G6), which plays an important role in immune infiltration, microenvironment, and immune escape, was constructed. It effectively predicts the survival of patients with KIRC.

Splenic Artery Embolization and Splenectomy for Spontaneous Rupture of Splenic Hemangioma and Its Imaging Features.

Background: Spontaneous splenic rupture (SSR) is a rare, often life-threatening, acute abdominal injury that requires immediate diagnosis and early treatment. SSR is mainly treated surgically or conservatively. A few cases of interventional embolization for SSRs have been reported. Case Presentation: A 30-year-old male patient complaining mainly of left upper abdominal pain underwent emergency abdominal computed tomography (CT) and showed enlargement of the spleen with a massive mixed-density shadow approximately 10.0 × 8.0 × 12.5 cm in size. The boundary was unclear and showed obvious progressive enhancement. Considering the intrasplenic tumor lesions with rupture and hemorrhage, the possibility of vascular tumors was high, with intraperitoneal blood and fluid accumulation. Digital subtraction angiography of the splenic arteriography and embolization of the ruptured splenic artery branches were performed. Postoperative hemoglobin progressively decreased, inflammatory indicators, such as white blood cell counts, procalcitonin (PCT), and C-reactive protein (CRP) were significantly increased, and 2 days after embolization, the patient developed severe hypoxemia, shock, pulmonary edema, and acute respiratory distress syndrome. CT re-examination 9 days after embolization showed reduced lesion absorption. After stabilization of the condition, splenectomy was performed, and postoperative platelet count increase, anticoagulant improvement, and discharge were observed. Postoperative pathological examination revealed extensive hemorrhage and necrosis, vascular tissue with abnormal hyperplasia in the surrounding area, vascular tissue in the bleeding area and outer wall (elastic fiber staining +), and local myofibroblast hyperplasia. Immunohistochemistry showed actin (SM +) and Ki67 (10% +). Conclusion: SSR caused by splenic hemangioma is rare, and the choice between surgical treatment or splenic artery embolization remains dependent on the patient's hemodynamic stability and imaging findings.

Clinical and Genetic Analysis of a Family With Sitosterolemia Caused by a Novel ATP-Binding Cassette Subfamily G Member 5 Compound Heterozygous Mutation.

Sitosterolemia (OMIM ##210250), also known as phytosterolemia, is a rare autosomal recessive disorder caused by mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) or member 8 (ABCG8) genes. This leads to abnormal functions of the transporter sterolin-1 protein encoded by ABCG5 and sterolin-2 protein encoded by ABCG8, respectively, which can hinder the formation of stable ABCG5/G8 heterodimers, decreasing its ability to transport sterols. As a result, phytosterols in tissue or plasma are significantly increased, leading to early onset atherosclerosis-related diseases and xanthelasma of tendons and skin. In this study, whole exome sequencing was performed on a Chinese Han proband with sitosterolemia to capture the target gene and screen for suspected pathogenic mutations. Sanger sequencing of the family members was performed to verify the relationship between family genetics and phenotypes. The structural and functional changes in the transporter sterolin-1 protein after the responsible mutation were predicted using bioinformatics analysis. A novel compound heterozygous mutation in the ABCG5 gene (NM_022436) was identified in a proband with sitosterolemia, one of which was inherited from the father: c.296T >G (p.M99R), and one from the mother: c.-76 C >T. SIFT, Polyphen2, and Mutation Taster software predicted that p.M99R may be the responsible variant and a novel variant. RNAFold software predicts that c.-76 C >T may affect the transcriptional information or the binding of RNA binding proteins by regulating the structure of RNA, and ultimately affect gene transcription or RNA stability and translation. Swiss model software predicts that the amino acid sequence around p.M99R is highly conserved, and p.M99R leads to instability of the tertiary structure of the ABCG5/ABCG8 heterodimer. GPS 5.0 predicted that M99R affects the phosphorylation of nearby amino acid sequences, and DUET and VarSite software predicted that M99R affects the stability of sterolin-1 and cause disease. The p.M99R and c.-76 C >T mutations led to the formation of unstable heterodimers, which disturbed sterol absorption and excretion in vivo. The compound heterozygous variants c.296 T >G (p.m99r) and C.-76 C >T on exon 3 of ABCG5 in this family may be the molecular genetic basis of sitosterolemia.

A Primary Extraskeletal Osteosarcoma of the Spleen: Rare Case Report.

Extraskeletal osteosarcoma is a rare malignant soft-tissue sarcoma that is difficult to diagnose. Surgery is a common treatment, although chemotherapy and radiotherapy are also used. Patients at risk of bleeding can undergo embolization combined with resection. The occurrence of primary splenic extraskeletal osteosarcoma in humans does not seem to have been reported in the literature. A 50-year-old woman who complained of pain in the left upper abdomen for 1 day was initially diagnosed with "splenic hemangioma with a high possibility of rupture and bleeding" and urgently underwent digital subtraction angiography, combined with splenic arteriography and embolization. Abdominal pain worsened 2 days postoperatively, with a hemoglobin level of 106.0 g/L. Consequently, emergency laparotomy combined with splenectomy was performed. The clinical and imaging features, pathological diagnosis, and embolization treatment of this case were analyzed retrospectively. CT of the upper abdomen revealed splenomegaly, an irregular low-density shadow in the spleen, and a flake-like calcification in the lateral margin of the left kidney. Nuclear MRI of the upper abdomen showed splenomegaly and a mass (approximately 8.4 cm × 5.7 cm × 6.3 cm) below the spleen with clear boundaries-this exhibited an uneven signal, which was slightly low in T1-weighted imaging (T1WI) and slightly high in T2-weighted imaging (T2WI). Several small cystic lesions or cystic cavities were observed in the mass, which exhibited a longer T2 signal. During the enhanced scan, the signal of the lesion showed progressive enhancement, and the enhancement range increased in the delayed phase scan, as well as a hematoma below the spleen capsule and calcification below the lesion (nodular T1WI/T2WI hypointense, approximately 3.3 cm × 3.6 cm). Postoperative biopsy pathology showed splenic soft tissue tumor: at low magnification, the multinucleated giant cells were scattered; at medium magnification, osteoclast-like multinucleated giant cells were observed; and at high magnification, lace- or grid-like tumor osteogenesis was detected. Immunohistochemistry showed that the expression of CD31, CD34, F8, s-100, desmin, SMA, and CD99 was negative, whereas the expression of ß-catenin, BCL-2, SATB-2, and P16 was positive. CD68 and MDM-2 showed low expression, while 50% of the cells were positive for Ki-67 expression. No abnormal concentration of radioactivity was found on the bone scan with 99mTc-MDP after the operation, further ruling out the occurrence of other bone tumors. The patient was diagnosed with primary extraskeletal osteosarcoma. It is necessary for multidisciplinary teams to diagnose malignant extraskeletal osteosarcomas.

Retrospective Analysis of the Effect of Lidocaine Combined with Methylprednisolone on Pain Control After Uterine Artery Embolization.

Background: The analgesic effect produced by the intra-arterial injection of lidocaine in patients undergoing uterine artery embolization has been proven to be safe and effective. Nevertheless, a significant degree of pain is typically experienced after the operation, and pain management is crucial. Methylprednisolone, which provides an anti-inflammatory effect, is widely used in the treatment of several diseases. To date, methylprednisolone has not been used after uterine artery embolization. Methods: A total of 131 patients with uterine leiomyoma were retrospectively enrolled. Forty-five patients (control group) were treated with embolized microspheres for bilateral uterine artery embolization. Fifty (study group) and 36 (lidocaine group) patients were administered lidocaine mixed with embolized microspheres during embolization, and in addition, the study group was administered methylprednisolone. Completed pain scales at different time points during surgery were obtained from patients undergoing uterine artery embolization. Efficacy against pain was evaluated by comparing the pain score, inflammatory index, and use of sufentanil within 24 h followed by a Kruskal-Wallis Test and a least significant difference post-hoc analysis. Results: The postoperative pain scores at 1, 4, and 7 h after uterine artery embolization in the study group (3.08 ± 2.09, 2.46 ± 1.93, and 2.38 ± 1.85, respectively) were significantly lower than those in the control group (4.84 ± 2.36, 4.16 ± 1.87, and 3.56 ± 1.93, respectively) and the lidocaine group (3.50 ± 2.10, 3.30 ± 1.88, and 3.28 ± 1.89, respectively). At the first 24 h after embolization, the total usage of sufentanil in the study group (31.4 ± 4.16) was significantly lower than those in the control group (45.7 ± 6.51) and the lidocaine group (38.3 ± 6.25). At 1 and 4 h, the pain scores of the lidocaine group were significantly lower than those of the control group. In addition, at the first 24 h after embolization, the total usage of sufentanil in the lidocaine group was significantly lower than that in the control group. Conclusion: Lidocaine in combination with methylprednisolone can significantly alleviate pain and reduce the usage of sufentanil after bilateral uterine artery embolization. Thus, methylprednisolone is a recommended addition to the therapeutic regimen after embolization.

Rare Cases of Bronchial Aneurysm and Comparison of Interventional Embolization in the Treatment of True Bronchial Aneurysm and Pseudobronchial Aneurysm.

Background: Bronchial artery aneurysm (BAA) is a rare disease. Rupture of BAA can lead to life-threatening hemoptysis, and once diagnosed, treatment is needed regardless of symptoms. Transcatheter artery embolization is the first choice of treatment because it is minimally invasive and effective. This study aimed to retrospectively compare the embolization treatment of a case of true BAA and that of a pseudobranchial aneurysm and explore the choice of embolization method for BAA with short neck or no neck. Materials and Methods: Embolization treatment and imaging characteristics of one case of true BAA and one case of pseudobronchial aneurysm admitted to our hospital were analyzed retrospectively. Embolization methods and therapeutic effects of two cases of BAAs were compared. Results: Case 1 was that of an intact true BAA inside the mediastinum located at the opening of the bronchial artery. The distal end of the aneurysm was embolized, and tumor cavity was occluded. No recurrence of BAA was found after the operation. Case 2 was that of a ruptured and hemorrhagic pseudobronchial aneurysm of the mediastinum. Coil embolization combined with covered stent graft exclusion of the thoracic aorta were performed, and the left bronchial artery and BAA were almost occluded. Nine months postoperatively, the mediastinal hematoma was almost completely absorbed. Conclusion: Endovascular embolization has become the most commonly used for the treatment of BAA. Different methods should be selected according to the location and nature of the aneurysm.

Clinical outcomes of uterine artery embolization and experience of postoperative transvaginal fibroid expulsion: a retrospective analysis.

PURPOSE: To explore the efficacy of uterine artery embolization (UAE) in the treatment of uterine fibroid and share the experience of transvaginal fibroid expulsion (FE) after UAE. METHODS: We retrospectively analyzed the changes in uterine and fibroid volume in 152 patients with symptomatic uterine fibroid after UAE at Fujian Provincial Hospital and Fujian Longyan People Hospital from March 2014 to March 2020. After a 12-month follow-up, the improvement in postoperative clinical symptoms and the incidence of complications were evaluated. We also shared the clinical features and imaging findings of four patients with FE after UAE. RESULTS: All 152 patients successfully underwent UAE. After a 12-month follow-up, the postoperative volumes of the uterus and fibroid at 3, 6, and 12 months were significantly reduced or disappeared compared to those before surgery (P < 0.05). Clinical symptoms, such as menorrhagia, dysmenorrhea, prolonged menstrual period, anemia, increased leucorrhea, pelvic discomfort, and urinary tract compression, were significantly improved after UAE. Among the 152 patients, the incidences of postoperative fever, nausea, vomiting, lower abdominal pain, and increased vaginal secretion were 7.89%, 7.24%, 3.95%, 19.08%, and 4.61%, respectively. Additionally, there were six cases of FE, with an incidence of 3.95%. Three cases of fibroid specimens and pathological images of fibroid biopsy, which were expelled through the vagina, were also provided. CONCLUSION: UAE is a satisfactory alternative surgical method for symptomatic uterine fibroid with definitive efficacy and high safety. However, it is necessary to guard against the occurrence of postoperative complications such as FE.

Different phenotypes of neurological diseases, including alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism, caused by de novo ATP1A3 mutation in a family.

BACKGROUND: The spectrum of neurological diseases related to ATP1A3 gene mutations is highly heterogeneous and exhibits different phenotypes. Phenotype overlaps, including alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy, and rapid-onset dystonia-parkinsonism (RDP), can also occur at extremely low incidences. Currently, over 90 types of pathogenic mutations have been identified in ATP1A3. PATIENTS AND METHODS: The family of a 2-year-11-month-old proband with AHC was recruited for this clinical investigation. The proband was screened for candidate mutation gene sites using next-generation sequencing and target-region capture technology. Sanger sequencing was used to identify carriers among family members. RESULTS: The mother of the proband with AHC was diagnosed with dystonia (later diagnosed as RDP). The biochemical and immune indices of the proband and the mother were not abnormal. Moreover, brain imaging of the proband revealed no significant abnormalities. However, the electroencephalogram of the mother was mildly abnormal, with no spike wave discharge. Brain MRI revealed slight cerebellar atrophy. Electromyography revealed neurogenic damage, with a decrease in the conduction velocity of the left ulnar and radial nerves. Based on the sequencing data, both the proband and her mother carried c.823G > C p. (Ala275Pro) heterozygotes; other family members were not identified as carriers. With a PolyPhen-2 score of 0.997 and SIFT score of 0.001, this mutation can be considered damaging. CONCLUSION: Family genotype-phenotype correlation analysis revealed that the phenotype and gene mutation were co-segregated, suggesting that it may be a pathogenic mutation.

A clinical analysis of intestinal mucosal necrosis and exfoliation induced by superior mesenteric vein thrombosis: A case report.

Background: Superior mesenteric vein (SMV) thrombosis is a rare intestinal ischemic disease. The clinical manifestations of patients differ, and most experience gastrointestinal symptoms. Case summary: A 45-year-old female patient presented with persistent abdominal pain and abnormal vaginal bleeding for 7 days. A physical examination revealed significant abdominal tenderness with positive rebound tenderness. A laboratory examination revealed a white blood cell count of 27 × 109/l, hemoglobin level of 52 g/L, and D-dimer of 4.54 mg/l. Enhanced computed tomography revealed a thickening and swelling of the jejunum and ileum in the left upper quadrant and portal vein. Filling defects in the main lumen and branch lumen suggested the possibility of portal vein and superior mesenteric vein thrombosis. Symptoms improved after treatment with low-molecular-weight heparin and warfarin. One month later, the patient developed occasional dull pain in the left lower quadrant, with long strips of discharge. An electronic colonoscopy revealed avascular necrosis and tissue exfoliation of the intestinal mucosa. After the continuation of warfarin therapy, the abdominal pain resolved. Five months later, the patient experienced recurrent abdominal pain and vomiting. A physical examination revealed a blood pressure of 75/49 mm Hg. An incomplete ileus with the portal and superior mesenteric vein thrombosis was diagnosed, partial jejunectomy and gastrointestinal bypass anastomosis were performed, and warfarin was continued postoperatively. Conclusion: The intestinal mucosal shedding observed, in this case, was caused by SMV thrombosis, which enriched the clinical manifestations of the disease and provided a new basis for the clinical diagnosis of SMV thrombosis.