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Background Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. Methods Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. Results The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. Conclusions The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

BackgroundBehçet’s disease (BD) is a unique autoimmune chronic systemic vasculitis that affects veins and arteries of all sizes. BD can lead to recurrent vascular events, especially venous thrombosis, with an incidence rate of 40%, or pseudoaneurysms formed under long-term inflammatory reaction or iatrogenic stimulation. BD-related risk factors promote endothelial dysfunction, platelet activation and overactivation of tissue factors leading to mural inflammatory thrombi. Thrombosis may be the first clinical manifestation of BD.Case presentationA 32-year-old man complaining of progressive swelling and pain in the right lower extremity for 30 days was initially diagnosed with “venous thrombosis of the right lower extremity,” using color Doppler ultrasonography. Patient underwent inferior vena cava filter placement combined with deep vein angioplasty of the right lower extremity and catheter-directed urokinase thrombolysis. Postoperative oral anticoagulant therapy was administered. However, the patient was readmitted 20 days later for pulsatile pain in the right groin. Prior medical history included 4 years of repeated oral and perineal ulcers, and 2 months of blurred vision. Abdominal computed tomography angiography (CTA) revealed rupture of the right common iliac artery (CIA) and left internal iliac artery (IIA), complicated by a pseudoaneurysm. Based on the clinical manifestations and other auxiliary examination results, the patient was re-diagnosed with “BD combined with deep venous thrombosis of the right lower extremity and an iliac artery pseudoaneurysm.” Stent implantation was performed for iliac artery pseudoaneurysm after symptoms were controlled with timely immunosuppressive therapy. After endovascular treatment, the patient underwent continued immunosuppressive therapy and dynamic reexaminations of abdominal CTA, which revealed that a small amount of contrast agent at the stent in the right CIA continued to flow into the cavity of the pseudoaneurysm; in addition, the size of the pseudoaneurysm was gradually increasing. Therefore, the patient underwent a second stent implantation for iliac artery pseudoaneurysm, and the condition improved further.ConclusionThe importance of early diagnosis of BD should be recognized, and the choice of interventional and surgical procedures should be carefully evaluated, as this may trigger further damage to vascular access in BD patients with aneurysm.

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 β-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.

The damage of podocytes is a primary hallmark of lupus nephritis (LN). Therefore, finding an effective way to inhibit the podocyte injury is important for improving the survival and development of patients with LN. Eucalyptus robusta exhibits anti-inflammatory properties. However, whether Formyl phloroglucinol meroterpenoids (FPMs), which are specialized metabolites of the genus Eucalyptus, is an anti-inflammatory active ingredient of E. robusta remains to be determined.This study asimed to identify novel FPMs from E. robusta and investigated their anti-inflammatory effects.Various separation methods were used to isolate and identify the compounds in the PE extract of E. robusta. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. The level of mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) of the podocyte cell line, MPC-5, were assessed using a multifunctional microplate reader combined with flow cytometry and fluorescence microscopy.Eight novel FPMs (1-8, Eucarbwenstols A-H, Fig. 1) and 15 known FPMs (9-23) were purified from the PE extract of E. robusta. It is noteworthy that compound 1 possesses an unprecedented FPM carbon skeleton. Among these compounds, compounds 1, 2, 4 and 5 showed the most promising potential for protecting MPC-5 cells because pretreatment with pro-inflammatory cytokines TGF-β, IFN-α and IL-6 decreased ROS production and ameliorated the mitochondrial state.Our research contributes to the characterization of E. robusta constituents and highlights the anti-inflammatory effects of FPMs.

Background. Brugada syndrome is a hereditary cardiac disease associated with mutations in ion channel genes. The clinical features include ventricular fibrillation, syncope, and sudden cardiac death. A family with Brugada syndrome with sudden cardiac death was analyzed to locate the associated mutation in the SCN5A gene. Methods and Results. Three generations of a Han Chinese family with Brugada syndrome were recruited in the study; their clinical phenotype data were collected and DNA samples extracted from the peripheral blood. Next-generation sequencing was carried out in the proband, and candidate genes and mutations were screened using the full exon capture technique. The family members who participated in the survey were tested for possible mutations using Sanger sequencing. Six family members were diagnosed with Brugada syndrome, including four asymptomatic patients. A newly discovered heterozygous mutation in the proband was located in exon 25 of SCN5A (NM_000335.5) at c.4313dup(p.Trp1439ValfsTer32). Among the surviving family members, only those with a Brugada wave on their electrocardiogram carried the c.4313dup(p.Trp1439ValfsTer32) variant. Bioinformatics prediction revealed that the frameshift of the c.4313dup (p.Trp1439ValfsTer32) mutant led to a coding change of 32 amino acids, followed by a stop codon, resulting in a truncated protein product. Conclusion. The newly discovered mutation site c.4313dup(p.Trp1439ValfsTer32) in exon 25 of SCN5A may be the molecular genetic basis of the family with Brugada syndrome.

Stretchable ultrasonic transducer arrays are capable of breaking through the limitations of rigid and flexible ultrasonic transducers for coupling interfaces, and can conform intimately to a variety of complex surfaces. However, structural design and fabrication processes are huge challenges in the development of stretchable ultrasonic transducer arrays. In this work, we proposed a stretchable ultrasonic linear array that was fabricated using rapid and convenient laser processing. The proposed single-layered and double-sided conductive stretchable electrode configuration eliminated the blockage of acoustic waves. The mechanical and acoustic properties of the linear array were demonstrated and the localization of the steel wire using the array was also performed.

The gut microbiota can affect human metabolism, immunity, and other biologic pathways through the complex gut-kidney axis (GKA), and in turn participate in the occurrence and development of kidney disease. In this study, 39 patients with stage 4-5 chronic kidney disease (CKD) and 40 healthy individuals were recruited and 16S rDNA sequencing was performed to analyze the V3-V4 conserved regions of their microbiota. A total of 795 operational taxonomic units (OTUs) shared between groups or specific to each group were obtained, among which 255 OTUs with significant differences between the two groups were identified (P

Hereditary distal renal tubular acidosis (dRTA) is a rare disease of H+ excretion defect of α-intercalated cells in renal collecting duct, caused by decreased V-ATPase function due to mutations in the ATP6V1B1 or ATP6V0A4 genes. In the present study, a genetic family with 5 members of the complete dRTA phenotype were found with distal tubule H+ secretion disorder, hypokalemia, osteoporosis, and kidney stones. A variant NM_020632.2:c.1631C > T (p.Ser544Leu) in exon 16 on an ATP6V0A4 gene associated with dRTA was detected by next generation sequencing target region capture technique and verified by Sanger sequencing, which suggested that except for one of the patients who did not receive the test, the other four patients all carried the p.S544L heterozygote. In transfected HEK293T cells, cells carrying p.S544L-mut showed early weaker ATPase activity and a slower Phi recovery rate after rapid acidification. By immunofluorescence localization, it was observed that the expression level of p.S544L-mut on the cell membrane increased and the distribution was uneven. Co-immunoprecipitation showed the a4 subunit of ATP6V0A4/p.S544L-mut could not bind to the B1 subunit, which might affect the correct assembly of V-ATPase. The present study of dRTA family suggests that the p.S544L variant may be inherited in a dominant manner.

The elastic and photocatalytic properties of multiferroic material InFeO3 under strain are calculated through density functional theory. The calculated results indicate that the intrinsic InFeO3 and the strained InFeO3 meet the mechanical stability conditions and hold a relatively larger elastic coefficient than popular multiferroic material BiFeO3. The calculated bandgap and band edge of InFeO3 under tensile strain show that InFeO3 could be a high-efficiency photocatalytic hydrogen production material. InFeO3 under tensile strain holds the ability of photocatalytic water splitting to produce hydrogen with excellent ferroelectric, mechanical properties and absorption of visible light.

With the algae play an important role in water eutrophication, a set of measuring system of water eutrophication based on the algae characteristic changes is designed, according to the relationship between the eutrophication and the algae characteristic changes. It is according to Canny self-adaptive edge detection algorithm, K-nearest neighbor classification algorithm, image processing technology, and the algae species and area’s changing, determined the status and level of water eutrophication pollution. The experiment result shows that the algae characteristic changes are realized and the water eutrophication is measured by the system. What’s more, the system has many advantages like adaptive, self-judgment and even good application value.