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Aprotic Li-O2 battery has attracted considerable interest for high theoretical energy density, however the disproportionation of the intermediate of superoxide (O2 - ) during discharge and charge leads to slow reaction kinetics and large voltage hysteresis. Herein, the chemically stable ruthenium tris(bipyridine) (RB) cations are employed as a soluble catalyst to alternate the pathway of O2 - disproportionation and its kinetics in both the discharge and charge processes. RB captures O2 - dimer and promotes their intramolecular charge transfer, and it decreases the energy barrier of the disproportionation reaction from 7.70 to 0.70â kcal mol-1 . This facilitates the discharge and charge processes and simultaneously mitigates O2 - and singlet oxygen related side reactions. These endow the Li-O2 battery with reduced discharge/charge voltage gap of 0.72â V and prolonged lifespan for over 230 cycles when coupled with RuO2 catalyst. This work highlights the vital role of superoxide disproportionation for Li-O2 battery.
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Morphological anisotropic engineering is powerful to synthesize metal-organic frameworks (MOFs) with versatile physicochemical properties for diverse applications ranging from gas storage/separation to electrocatalysis and batteries, etc. Herein, we developed a carbon substrate guided strategy to manipulate the facet-dependent coordination for morphology engineering of Fe-THBQ (tetrahydroxy-1,4-benzoquinone) frameworks, which is built with cubic Fe octamer bridged by two parallel THBQ ligands along three orthogonal axes, extending to a three-dimensional (3D) framework with pcu-e network topology. The electronegative O-containing functional groups on carbon surfaces compete with THBQ linkers to selectively interact with the unsaturated coordinated Fe cations on the {111} facets and inhibit crystal growth along the <111> direction. The morphology of Fe-THBQ evolves from thermodynamically favored truncated cube to cuboctahedron depending on the content of O-containing functional groups on the carbon substrate. The Fe-THBQ with varied morphologies exhibits facet-dependent performances for electrochemical lithium storage. This work will shed light on the morphology modulation of MOFs for promising applications.
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Electrochemical CO2 reduction to liquid multi-carbon alcohols provides a promising way for intermittent renewable energy reservation and greenhouse effect mitigation. Cuδ+ (0<δ<1) species on Cu-based electrocatalysts can produce ethanol, but the in situ formed Cuδ+ is insufficient and easily reduced to Cu0 . Here a Cu2 S1-x catalyst with abundant Cuδ+ (0<δ<1) species is designedly synthesized and exhibited an ultralow overpotential of 0.19â V for ethanol production. The catalyst not only delivers an outstanding ethanol selectivity of 86.9 % and a Faradaic efficiency of 73.3 % but also provides a long-term stability of Cuδ+ , gaining an economic profit based on techno-economic analysis. The calculation and in situ spectroscopic results reveal that the abundant Cuδ+ sites display electron-donating ability, leading to the decrease of the reaction barrier in the potential-determining C-C coupling step and eventually making the applied potential close to the theoretical value.
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PURPOSE: Esophageal carcinoma (EC) is one of the most aggressive type cancers and dysregulation of retinoid X receptor α (RXRα) involves various tumors. However, the relationship of RXRα with the clinicopathological factors of EC, particularly prognostic characteristics, remains unclear. This present study was to evaluate the effect of RXRα expression in the development of EC. METHODS: The mRNA and protein expression level of RXRα in EC and normal esophageal tissues using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The subcellular localization was detected by immunohistochemistry (IHC) analysis. The clinicopathological parameters were included age, sex, tumor size, differentiation, TNM stages and lymph node metastasis. Kaplan-Meier method and Cox's regression analyses were performed to evaluate the prognosis of 60 patients with EC. RESULTS: RXRα was elevated in EC tissues comparing with normal esophageal tissues at both mRNA and protein levels. The overexpression level of RXRα was closely associated to the tumor differentiation, TNM stage and lymph node metastasis of patients with EC. In addition, EC patients with RXRα high expression had significantly lower disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed RXRα expression as an independent predictor for the DFS and OS rate of patients with EC. CONCLUSIONS: Our results showed that overexpression of RXRα was correlated with unfavorable prognosis, suggesting that RXRα may serve as a potential targeted therapeutic marker in the treatment of EC.
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Biomarcadores de Tumor/metabolismo , Neoplasias Esofágicas/diagnóstico , Receptor alfa X Retinoide/metabolismo , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Receptor alfa X Retinoide/genéticaRESUMEN
Sickle cell trait (SCT) has classically been categorized as a benign condition except in rare cases or upon exposure to severe physical conditions. However, several lines of evidence indicate that individuals with SCT are not always asymptomatic, and additional physiological changes and risks may remain unexplored. Here, we utilized mice harbouring one copy of normal human ß globin and one copy of sickle human ß globin as a model of SCT to assess haematological, histopathological and somatosensory outcomes. We observed that SCT mice displayed renal and hepatic vascular congestion after exposure to hypoxia. Further, we observed that SCT mice displayed increased cold aversion as well as mechanical and heat sensitivity, though to a lesser degree than homozygous sickle cell disease mice. Notably, mechanical hypersensitivity increased following hypoxia and reoxygenation. Overall our findings suggest that SCT is not entirely benign, and further assessment of pain and cutaneous sensitization is warranted both in animal models and in clinical populations.
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Viscosidad Sanguínea , Hipoxia , Rasgo Drepanocítico/fisiopatología , Trastornos Somatosensoriales , Animales , Frío , Modelos Animales de Enfermedad , Calor , Humanos , Ratones , Fenómenos Fisiológicos de la PielRESUMEN
High mobility group box 1 (HMGB1) is a chromatin-binding protein that maintains DNA structure. On cellular activation or injury, HMGB1 is released from activated immune cells or necrotic tissues and acts as a damage-associated molecular pattern to activate Toll-like receptor 4 (TLR4). Little is known concerning HMGB1 release and TLR4 activity and their role in the pathology of inflammation of sickle cell disease (SCD). Circulating HMGB1 levels were increased in both humans and mice with SCD compared with controls. Furthermore, sickle plasma increased HMGB1-dependent TLR4 activity compared with control plasma. HMGB1 levels were further increased during acute sickling events (vasoocclusive crises in humans or hypoxia/reoxygenation injury in mice). Anti-HMGB1 neutralizing antibodies reduced the majority of sickle plasma-induced TLR4 activity both in vitro and in vivo. These findings show that HMGB1 is the major TLR4 ligand in SCD and likely plays a critical role in SCD-mediated inflammation.
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Anemia de Células Falciformes/metabolismo , Proteína HMGB1/metabolismo , Inflamación/metabolismo , Receptor Toll-Like 4/metabolismo , Anemia de Células Falciformes/inmunología , Animales , Regulación de la Expresión Génica , Humanos , Hipoxia/patología , Ligandos , Ratones , Ratones Endogámicos C57BL , Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Humans and mice with sickle cell disease (SCD) have rigid red blood cells (RBCs). Omega-3 fatty acids, such as docosahexanoic acid (DHA), may influence RBC deformability via incorporation into the RBC membrane. In this study, sickle cell (SS) mice were fed natural ingredient rodent diets supplemented with 3% DHA (DHA diet) or a control diet matched in total fat (CTRL diet). After 8weeks of feeding, we examined the RBCs for: 1) stiffness, as measured by atomic force microscopy; 2) deformability, as measured by ektacytometry; and 3) percent irreversibly sickled RBCs on peripheral blood smears. Using atomic force microscopy, it is found that stiffness is increased and deformability decreased in RBCs from SS mice fed CTRL diet compared to wild-type mice. In contrast, RBCs from SS mice fed DHA diet had markedly decreased stiffness and increased deformability compared to RBCs from SS mice fed CTRL diet. Furthermore, examination of peripheral blood smears revealed less irreversibly sickled RBCs in SS mice fed DHA diet as compared to CTRL diet. In summary, our findings indicate that DHA supplementation improves RBC flexibility and reduces irreversibly sickled cells by 40% in SS mice. These results point to potential therapeutic benefits of dietary omega-3 fatty acids in SCD.
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Anemia de Células Falciformes/dietoterapia , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Membrana Eritrocítica/efectos de los fármacos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/patología , Animales , Modelos Animales de Enfermedad , Recuento de Eritrocitos , Deformación Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/patología , Humanos , Ratones , Ratones Endogámicos C57BL , Microscopía de Fuerza AtómicaRESUMEN
Layered transition-metal (TM) oxide cathodes have attracted growing attention in sodium-ion batteries (SIBs). However, their practical implementation is plagued by Jahn-Teller distortion and irreversible cation migration, leading to severe voltage decay and structure instability. Herein, O3-Na0.898K0.058Ni0.396Fe0.098Mn0.396Ti0.092O2 (KT-NFM) is reported as an ultrastable cathode material via multisite substitution with rigid KO6 pillars and flexible TiO6 octahedra. The K pillars induce contracted TMO2 slabs and their strong Coulombic repulsion to inhibit Ni/Fe migration; and Ti incorporation reinforces the hybridization of Ni(3deg*)-O(2p) to mitigate the undesired O3-O'3 phase transition. These enable the reversible redox of Ni2+âNi3 . 20+ and Fe3+âFe3.69+ for 138.6 mAh g-1 and ultrastable cycles with >90% capacity retention after 2000 cycles in a pouch cell of KT-NFM||hard carbon. This will provide insights into the design of ultrastable layered cathode materials of sodium-ion batteries and beyond.
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We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which fetal loss is triggered when the maternal prothrombotic state coincides with fetal gene defects that reduce activation of the protein C anticoagulant pathway within the placenta. Fetal loss is caused by disruption of placental morphogenesis at the stage of labyrinth layer formation and occurs in the absence of overt placental thrombosis, infarction, or perfusion defects. Platelet depletion or elimination of protease-activated receptor 4 (Par4) from the mother allows normal placentation and prevents fetal loss. These findings establish a cause-effect relationship for the observed epidemiologic association between maternal FvL status and fetal loss and identify fetal gene defects as risk modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is mediated by Par4-dependent activation of maternal platelets at the fetomaternal interface and likely involves a pathogenic pathway independent of occlusive thrombosis. Our results further demonstrate that the interaction of two given thrombosis risk factors produces markedly disparate consequences on disease manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed in which this interaction occurs.
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Resistencia a la Proteína C Activada/complicaciones , Plaquetas/metabolismo , Modelos Animales de Enfermedad , Factor V/genética , Muerte Fetal/etiología , Enfermedades Fetales/genética , Placenta/patología , Resistencia a la Proteína C Activada/genética , Animales , Femenino , Muerte Fetal/patología , Ratones , Ratones Endogámicos C57BL , Placenta/irrigación sanguínea , Mutación Puntual/genética , Embarazo , Resultado del Embarazo/genética , Receptores de Trombina/metabolismo , Factores de Riesgo , Trombomodulina/genéticaRESUMEN
In mice lacking the blood coagulation regulator thrombomodulin, fibrinolytic degradation products (FDP) of fibrin induce apoptotic cell death of a specialized cell type in the placenta, polyploid trophoblast giant cells. Here, we document that this bioactivity of FDP is conserved in human FDP, is not limited to trophoblast cells, and is associated with an Aalpha-chain segment of fibrin fragment E (FnE). The majority of proapoptotic activity is arginine-glycine-aspartic acid (RGD)-independent and requires caveolin-1-dependent cellular internalization of FnE. Internalization through caveoli is mediated by an epitope contained within Aalpha52-81 that is necessary and sufficient for cellular uptake of FnE. Aalpha52-81 does not cause apoptosis itself, and competitively inhibits FnE internalization and apoptosis induction. Apoptotic activity per se resides within Aalpha17-37 and requires the N-terminal neoepitope generated by release of fibrinopeptide A. Cellular internalization of FnE elicits depression of mitochondrial function and consequent apoptosis that is strictly dependent on the activity of caspases 9 and 3. These findings describe the molecular details of a novel mechanism linking fibrin degradation to cell death in the placenta, which may also contribute to pathologic alterations in nonplacental vascular beds that are associated with fibrinolysis.
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Apoptosis , Caveolina 1/fisiología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Animales , Aorta/citología , Aorta/metabolismo , Caspasa 3/metabolismo , Células Cultivadas , Coriocarcinoma/metabolismo , Coriocarcinoma/patología , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Glutatión Transferasa/genética , Humanos , Etiquetado Corte-Fin in Situ , Ratones , Ratones Noqueados , Fragmentos de Péptidos/metabolismo , Embarazo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismo , Venas Umbilicales/citología , Venas Umbilicales/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologíaRESUMEN
Spectrin is the backbone of the erythroid cytoskeleton; sph/sph mice have severe hereditary spherocytosis (HS) because of a mutation in the murine erythroid alpha-spectrin gene. sph/sph mice have a high incidence of thrombosis and infarction in multiple tissues, suggesting significant vascular dysfunction. In the current study, we provide evidence for both pulmonary and systemic vascular dysfunction in sph/sph mice. We found increased levels of soluble cell adhesion molecules in sph/sph mice, suggesting activation of the vascular endothelium. We hypothesized that plasma hemoglobin released by intravascular hemolysis initiates endothelial injury through nitric oxide (NO) scavenging and oxidative damage. Likewise, electron paramagnetic resonance spectroscopy showed that plasma hemoglobin is much greater in sph/sph mice. Moreover, plasma from sph/sph mice had significantly higher oxidative potential. Finally, xanthine oxidase, a potent superoxide generator, is decreased in subpopulations of liver hepatocytes and increased on liver endothelium in sph/sph mice. These results indicate that vasoregulation is abnormal, and NO-based vasoregulatory mechanisms particularly impaired, in sph/sph mice. Together, these data indicate that sph/sph mice with severe HS have increased plasma hemoglobin and NO scavenging capacity, likely contributing to aberrant vasoregulation and initiating oxidative damage.
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Hemólisis , Espectrina/genética , Esferocitosis Hereditaria/fisiopatología , Vasodilatación , Animales , Modelos Animales de Enfermedad , Hemoglobinas , Hipertensión Pulmonar , Hígado/citología , Ratones , Ratones Mutantes , Óxido Nítrico , Xantina OxidasaRESUMEN
A series of novel boat-shaped host-guest complexes were designed and synthesized by the combination of a new calixarene fragment-based tetraphosphine ligand L with group 11 metal salts Cu(MeCN)4ClO4 and AgNO3 in a self-assembly process, and by the following anion exchange reactions of complex 1 with sodium p-toluenesulfonate, AcONa, PhCO2Na and sodium 9-anthrylcarboxylate. The host with a novel boat-shaped cavity is capable of self-adaptive encapsulation of various anions of different sizes through M(i)-O coordinations and CHπ interactions between the host and guest anion. The DFT calculations confirmed that the CHπ interaction played a vital role in the self-adaptive phenomenon in complexes 4-6.
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The trafficking of T-lymphocytes to peripheral draining lymph nodes is crucial for mounting an adaptive immune response. The role of chemokines in the activation of integrins via Ras-related small GTPases has been well established. R-Ras is a member of the Ras-subfamily of small guanosine-5'-triphosphate-binding proteins and its role in T cell trafficking has been investigated in R-Ras null mice (Rras-/-). An examination of the lymphoid organs of Rras-/- mice revealed a 40% reduction in the cellularity of the peripheral lymph nodes. Morphologically, the high endothelial venules of Rras-/- mice were more disorganized and less mature than those of wild-type mice. Furthermore, CD4+ and CD8+ T cells from Rras-/- mice had approximately 42% lower surface expression of L-selectin/CD62L. These aberrant peripheral lymph node phenotypes were associated with proliferative and trafficking defects in Rras-/- T cells. Furthermore, R-Ras could be activated by the chemokine, CCL21. Indeed, Rras-/- T cells had approximately 14.5% attenuation in binding to intercellular adhesion molecule 1 upon CCL21 stimulation. Finally, in a graft-versus host disease model, recipient mice that were transfused with Rras-/- T cells showed a significant reduction in disease severity when compared with mice transplanted with wild-type T cells. These findings implicate a role for R-Ras in T cell trafficking in the high endothelial venules during an effective immune response.
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Movimiento Celular/fisiología , Enfermedad Injerto contra Huésped/inmunología , Molécula 1 de Adhesión Intercelular/metabolismo , Linfocitos T/metabolismo , Proteínas ras/metabolismo , Animales , Adhesión Celular/inmunología , Movimiento Celular/genética , Proliferación Celular , Quimiocina CCL21/metabolismo , Activación Enzimática , Femenino , Selectina L/biosíntesis , Selectina L/metabolismo , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Antígeno-1 Asociado a Función de Linfocito/biosíntesis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Unión Proteica , Bazo/citología , Linfocitos T/trasplante , Proteínas ras/genéticaRESUMEN
Lipoblastoma is a rare benign mesenchymal tumor that composes of embryonal white fat tissue and typically occurs in infants or young children under 3 years of age. It usually affects the extremities, trunk, head, and neck. The perineum is a rare location with only 7 cases reported in the literature. We describe a case of 3-year-old girl with a lipoblastoma arising from perineum. An approximately 4.5 cm × 3.5 cm × 2.5 cm nodule was resected in left perineum with satisfied results. Pathological examination showed that it was composed of small lobules of mature and immature fat cells, separated by fibrous septa containing small dilated blood vessels. The left perineal lipoblastoma, although rare, should be differentiated from some other mesenchymal tumors with similar histologic and cytological features.
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Lipoblastoma/patología , Perineo/patología , Biomarcadores de Tumor/análisis , Preescolar , Femenino , Humanos , InmunohistoquímicaRESUMEN
A 42-year-old male presented right upper abdomen pain for more than 6 days, which misdiagnose calculus of intrahepatic duct and acute cholecystitis. An approximately 1.5 cm x 1.0 cm x 1.0 cm nodule was found and resected in left lateral lobe of hepatic. Pathological examination showed spindle cell and fibroblast -like cells within the collagenous stroma. Immunohistochemically, these spindle tumor cells showed diffuse Vim and Bcl-2 positive reactivity, but S-100 protein and HMB45 were negative. The post-operative course was uneventful. Solitary fibrous tumors of the liver, although rare, should be differentiated from mesenchymal lesions of the liver. Virtual slide: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4214341041091088.
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Neoplasias Hepáticas/patología , Tumores Fibrosos Solitarios/patología , Dolor Abdominal/etiología , Adulto , Biomarcadores de Tumor/análisis , Biopsia , Pancreatocolangiografía por Resonancia Magnética , Diagnóstico Diferencial , Hepatectomía , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/química , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Masculino , Valor Predictivo de las Pruebas , Tumores Fibrosos Solitarios/química , Tumores Fibrosos Solitarios/complicaciones , Tumores Fibrosos Solitarios/cirugía , Resultado del TratamientoRESUMEN
Patients with concussion often present with temporary disturbance of consciousness. The microstructural and functional changes in the brain associated with concussion, as well as the relationship with transient cognitive disorders, are currently unclear. In the present study, a rabbit model of simple concussion was established. Magnetic resonance-diffusion tensor imaging results revealed that the corona radiata and midbrain exhibited significantly decreased fractional anisotropy values in the neural pathways associated with memory and the reticular formation. In addition, the apparent diffusion coefficient values were significantly increased following injury compared with those before injury. Following a 1-hour period of quiet rest, the fractional anisotropy values significantly increased, and apparent diffusion coefficient values significantly decreased, returning to normal pre-injury levels. In contrast, the fractional anisotropy values and apparent diffusion coefficient values in the corpus callosum, thalamus and hippocampus showed no statistical significant alterations following injury. These findings indicate that the neural pathways associated with memory and the reticular formation pathway exhibit reversible microstructural white matter changes when concussion occurs, and these changes are exhibited to a different extent in different regions.
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Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm × 50 mm × 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease.
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Carcinoma de Células Pequeñas/diagnóstico , Epiplón/patología , Carcinoma de Células Pequeñas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , UltrasonografíaRESUMEN
Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm of low malignant potential that mostly affects young women in the second or third decade of life. The number of such patients reported in the literature has increased in recent years, while SPT in pregnancy is extremely rare. To the best of our knowledge, only one case of SPT in pregnancy has been reported in the English-language literature. We herein report a case of asymptomatic SPT in a 26-year-old Chinese female in the 14th week of pregnancy, and present our experience of the surgical management of SPT in pregnancy.