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Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.
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Aeromonas hydrophila , Yema de Huevo , Enfermedades de los Peces , Inmunoglobulinas , Vibriosis , Vibrio , Animales , Inmunoglobulinas/inmunología , Inmunoglobulinas/sangre , Vibriosis/veterinaria , Vibriosis/inmunología , Vibriosis/prevención & control , Vibrio/inmunología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/prevención & control , Yema de Huevo/inmunología , Aeromonas hydrophila/inmunología , Carpa Dorada/inmunología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Inmunización Pasiva/veterinaria , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificaciónRESUMEN
Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1ß) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.
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Pseudomonas fluorescens , Vacunas , Animales , Proteínas de la Membrana , Yema de Huevo , Antioxidantes/análisis , Inmunoglobulinas , Anticuerpos , Inflamación , PollosRESUMEN
BACKGROUND: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. METHODS: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. RESULTS: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. CONCLUSIONS: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.
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Microbioma Gastrointestinal , Humanos , Femenino , Embarazo , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Heces/microbiología , Ácidos y Sales Biliares , HipoxantinasRESUMEN
Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.
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Objective:To investigate the malignant potential of histopathological class B3 and B5a lesions by ultrasound-guided core needle biopsy (CNB).Methods:Retrospective analysis of the histopathological results of 712 breast lesions that successively underwent CNB process and surgical resection in the Shanghai General Hospital from January 2018 to December 2022, of which 47 lesions were reported as class B3 and 70 lesions as class B5a.Results:CNB identified 47 category B3 lesions, comprising 19 cases of atypical ductal hyperplasia, 17 papillary lesions, 8 phyllodes tumors, and 3 complex sclerosing lesions. Of these cases, surgical pathology was in full agreement with CNB pathology in 27 instances, indicating a concordance rate of 57.4% (27/47) and an inconsistency rate of 42.6% (20/47). Out of the 20 inconsistent cases, 70.0% (14/20) were upgraded based on the findings from the surgical pathology.Specifically, 4 cases of atypical ductal hyperplasia and 2 cases of intraductal papilloma were upgraded to invasive breast cancer (B5b) after surgery. Among the 4 cases with puncture pathology indicating atypical ductal hyperplasia and one complex sclerosing lesion, these five lesions were upgraded to ductal carcinoma in situ (B5a) after surgery. Two puncture pathologies were diagnosed as atypical ductal hyperplasia, and these were upgraded to ductal carcinoma in situ with microinvasion (B5b) after surgery. One puncture pathology indicated a borderline phyllodes tumor, and this was upgraded to malignant phyllodes tumor (B5b) after surgery. And 30.0% (6/20) resulted in downgrade after surgery, specifically 4 cases of atypical ductal hyperplasia, which were downgraded to breast adenopathy (B2). Of these, 1 puncture pathology was identified as atypical ductal hyperplasia and one as a borderline phyllodes tumor, which were both downgraded to fibroadenoma (B2). Seventy lesions were diagnosed as B5a lesions by CNB pathology, with 28 of them showing complete concurrence with the surgical pathology, a concordance rate of 40.0% (28/70), and an inconsistency rate of 60.0% (42/70). Of the 42 cases with discrepancies, all 42 were upgraded, yielding an upgrading rate of 100% (42/42). Of these, 21 were upgraded to ductal carcinoma in situ with microinvasion (B5b) and 21 to invasive breast cancer (B5b).Conclusions:Lesions with CNB pathology in categories B3 and B5a have a high rate of postoperative escalation. B3 and B5a lesions should be treated with considerable care, especially atypical ductal hyperplasia, which should be surgically resected, and CNB examination should be performed twice if necessary.
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Objective:To explore the clinical features, treatment, prognosis and genetic mutation in neonatal congenital hyperinsulinemia(CHI).Methods:Neonates with CHI admitted to the neonatal intensive care unit of Hebei Provincial Children′s Hospital from February 2017 to August 2020 were selected, and their clinical characteristics, diagnosis and treatment, prognosis and genetic mutation were retrospectively analyzed.Results:A total of seven neonates were enrolled.The average gestational age was(38.1±1.5)weeks with two cases gestational age<37 weeks.The mean birth weight was(3 608±906)g with three cases birth weight>4 000 g. The common clinical manifestations included lethargy, poor feeding, cyanosis, seizures, and tremble.Non-specific manifestations were observed in two premature infants, whose blood glucose were found very low during the routine monitoring at 1 hour and 3 hours after birth respectively.Among the seven cases, six cases needed high glucose infusion rate(GIR)[>10 mg/(kg·min)] to maintain the serum glucose at the normal level from the beginning.Only one case needed lower GIR[3-5 mg/(kg·min)] on admission while gradually increased to 8 mg/(kg·min) maximumly during hospitalization.All seven neonates were treated with diazoxide orally, and two cases(2/7) were effective, including one case who discontinued the drug at six months after birth with normal blood glucose level.The remaining five neonates(5/7) were diazoxide resistant due to mutations in the ABCC8 gene encoding the K ATP+ -channel of the pancreatic beta cell and then treated with octreotide.Two cases(2/5) of them were effective to octreotide and the other three cases(3/5) were both diazoxide and octreotide resistant.One case died after withdrawal from the treatment and the other one lost follow-up.The other five cases were followed up until now.Normal neurological development were found in three cases.Two cases were found with epilepsy and moderate developmental delay in language and social competence ability during the follow up.Mutations in ABCC8 were the most common in seven cases, of which six cases were heterozygous mutation of ABCC8 and one case was heterozygous mutation of GLUDI. Conclusion:The clinical manifestations of CHI are non-specific.The blood glucose level of the high-risk neonates should be timely monitored.Neonates who needs lower GIR[<8 mg/(kg·min)] at the early stage can not be completely excluded CHI.Some CHI cases may self-resolved after several months.Molecular diagnosis can identify the pathogenic genes, which is important to achieve accurate diagnosis and treatment, and thus improve the prognosis of patients with CHI.
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Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.
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This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
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Humanos , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Asteraceae/química , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
Among aquaculture vaccines, polyvalent vaccines (for immunoprotection against multiple bacterial species) are more efficient and can better avoid bacterial resistance and antibiotic residues in fish. Here, 15 outer membrane proteins (OMPs) of Aeromonas hydrophila were cloned and purified, and mouse antisera were prepared. Passive immunization to Carassius auratus showed that four OMPs sera (OmpW, OmpAII, P5, and AHA2685) and the entire OMPs serum held effective immunoprotection against A. hydrophila infection. Furthermore, the active immunization of four OMPs to C. auratus showed that OmpW, OmpAII, P5, and AHA2685 held effective immunoprotection against A. hydrophila, and OmpW held active cross-protection against Vibrio alginolyticus. The mechanisms of these four candidate vaccines in triggering immune responses were subsequently explored. They all could activate innate immune responses in active immunization, down-regulate (p < 0.05) the inflammation-related genes expression to reduce the inflammatory reaction induced by A. hydrophila, and down-regulate (p < 0.05) antioxidant-related factors to reduce the antioxidant reaction for bacterial infection. Noteablely, the four OMPs had protective abilities on kidney and spleen tissues of C. auratus after challenged with A. hydrophila and V. alginolyticus by histopathological observation. Collectively, our results identify OmpW as a polyvalent vaccine candidate, and OmpAII, P5, and AHA2685 as vaccine candidates against A. hydrophila infection in fish.
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Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Enfermedades de los Roedores , Aeromonas hydrophila , Animales , Antibacterianos , Antígenos Bacterianos , Antioxidantes , Proteínas de la Membrana Bacteriana Externa , Vacunas Bacterianas , Carpas/metabolismo , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Sueros Inmunes , Ratones , Vacunas CombinadasRESUMEN
BACKGROUND: The optimal width of resection margin (RM) for hepatocellular carcinoma (HCC) remains controversial. This study aimed to investigate the value of imaging tumor capsule (ITC) and imaging tumor size (ITS) in guiding RM width for patients with HCC. METHODS: Patients who underwent hepatectomy for HCC in our center were retrospectively reviewed. ITC (complete/incomplete) and ITS (≤ 3 cm/> 3 cm) were assessed by preoperative magnetic resonance imaging (MRI). Using subgroup analyses based on ITC and ITS, the impact of RM width [narrow RM (< 5 mm)/wide RM (≥ 5 mm)] on recurrence-free survival (RFS), overall survival (OS), and RM recurrence was analyzed. RESULTS: A total of 247 patients with solitary HCC were included. ITC and ITS were independent predictors for RFS and OS in the entire cohort. In patients with ITS ≤ 3 cm, neither ITC nor RM width showed a significant impact on prognosis, and the incidence of RM recurrence was comparable between the narrow RM and wide RM groups (15.6% vs. 4.3%, P = 0.337). In patients with ITS > 3 cm and complete ITC, the narrow RM group exhibited comparable RFS, OS, and incidence of RM recurrence with the wide RM group (P = 0.606, 0.916, and 0.649, respectively). However, in patients with ITS > 3 cm and incomplete ITC, the wide RM group showed better RFS and OS and a lower incidence of RM recurrence compared with the narrow RM group (P = 0.037, 0.018, and 0.046, respectively). CONCLUSIONS: As MRI-based preoperative markers, conjoint analysis of ITC with ITS aids in determining RM width for solitary HCC patients. Narrow RM is applicable in patients with ITS ≤ 3 cm regardless of ITC status and in those with ITS > 3 cm and complete ITC. Wide RM is preferred in those with ITS > 3 cm and incomplete ITC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Márgenes de Escisión , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Hepatectomía/efectos adversos , Hepatectomía/métodos , PronósticoRESUMEN
Objective:To study the clinical features of neonatal hyperthyroidism.Methods:From September 2013 to September 2020, clinical data of neonates with hyperthyroidism admitted to the neonatal intense care unit of our hospital were retrospectively collected and analyzed.Results:A total of 7 neonates were included. The average gestation age was (35.8±2.3) weeks with 5 cases had GA<37 weeks. The median age of diagnostic was 16 d (7~18 d). The common clinical manifestations included tachycardia, irritability, low-grade fever, hyperhidrosis, bulimia, poor weight gain, diarrhea and jaundice. The levels of serum free triiodothyronine (FT 3) and thyroxine (FT 4) were elevated in all 7 cases and thyroid stimulating hormone (TSH) were decreased. The Doppler ultrasound of thyroid gland in two neonates revealed enlarged thyroid gland with abundant blood flow. All 7 mothers had hyperthyroidism with 4 mothers provided the history of hyperthyroidism and the other 3 were also confirmed after their infants were diagnosed. All 7 infants were treated with anti-thyroid drugs (ATD) and 2 were additionally given β-blockers to control heart rate. The median ATD duration was 40 d (7~58 d). 2 cases (both preterm infants) had slight decrease in FT 4 during medication. FT 4 of all 7 cases returned to normal before TSH. Conclusions:Neonatal hyperthyroidism has various and nonspecific clinical manifestations. Early diagnosis and timely treatment are important to prevent short-term and long-term adverse outcomes. Whether their mothers provide definite history of thyroid disorder or not, the thyroid function of the suspected neonates should be carefully monitored.
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OBJECTIVE: To evaluate the influence of crown coverage of surgical guides on the accuracy of static computer-assisted implant surgeries (sCAISs) in different partially edentulous situations. METHODS: Acrylic models with five types of partially edentulous situations were fabricated in this study. In coDiagnostiX software (Dental Wings, Montreal, Canada), surgical templates were designed and fabricated with reduced crown coverage (RCC), standard crown coverage (SCC) and extended crown coverage (ECC). Then, fully guided implant placement into the acrylic models was performed by dental surgeons with more than 10 years of experience. In total, 120 models and 120 guides were manufactured, and 168 bone-level Straumann replica implants (4.1 × 10 mm, Institut Straumann AG, Basel, Switzerland) were inserted. Postoperative implant positions were scanned (Trios 3, 3 shape, Copenhagen, Denmark) and compared with the preplanned virtual positions via coDiagnostiX (Dental Wings, Montreal, Canada). The angular, coronal and apical deviations were measured and analyzed to evaluate the accuracy of implant insertion. Statistical analysis was performed using one-way ANOVA and Tukey's test. RESULTS: For single tooth missing situations, the RCC group was similar to the SCC group and ECC group in anterior sites. In premolar or molar sites, the SCC and ECC groups had no statistically significant difference (p > .05), while the RCC group had more coronal and apical deviation (p < .05). For multiple teeth missing situations, there was no difference among the RCC, SCC and ECC groups (p > .05). No difference was found among the five edentulous situations with different CCs (p > .05). CONCLUSION: The CC of templates can significantly affect the accuracy of guided surgeries when implants are inserted in a single gap at posterior sites. Templates with CC extended to the undercut line may be an optimal choice for static guided surgeries. CLINICAL SIGNIFICANCE: The accuracy of static guided implant surgery can be influenced by the CC of templates, and proper CC with the guide covering extending to the undercut line may contribute to improved accuracy. CC should be taken into consideration when designing surgical templates.
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Implantación Dental Endoósea , Implantes Dentales , Diseño Asistido por Computadora , Tomografía Computarizada de Haz Cónico , Coronas , Imagenología TridimensionalRESUMEN
BACKGROUND: Many sports and physical activities can result in lower limb injures. Pedaling is an effective exercise for lower extremity rehabilitation, but incorrect technique may cause further damage. To some extent, previous experiments have been susceptible to bias in the sample recruited for the study. Alternatively, methods used to simulation activities can enable parametric studies without the influence of noise. In addition, models can facilitate the study of all muscles in the absence of the effects of fatigue. This study investigated the effects of crank length on muscle behavior during pedaling. METHODS: Six muscles (soleus, tibialis anterior, vastus medialis, vastus lateralis, gastrocnemius, and rectus femoris), divided into three groups (ankle muscle group, knee muscle group, and biarticular muscle group), were examined under three cycling crank lengths (100 mm, 125 mm, and 150 mm) in the present study. In addition, the relationship between crank length and muscle biological force was analyzed with the AnyBody Modeling System™, a human simulation modeling software based on the Hill-type model. Findings. Based on inverse kinematic analysis, the results indicate that muscle activity and muscle force decrease in varying degrees with increases in crank length. The maximum and minimum muscular forces were attained in the tibialis anterior and vastus lateralis, respectively. Interpretation. Studying the relationship between muscle and joint behavior with crank length can help rehabilitation and treating joint disorders. This study provides the pedal length distribution areas for patients in the early stages of rehabilitation.
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Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. The aberrant activation of STAT3 commonly occurs in GBM and is a key player in GBM tumorigenesis. Yet, the aberrant activation of STAT3 signaling is not fully understood. Here, we report that SH2B adaptor protein 3 (SH2B3) is highly expressed in GBM and preferentially expressed in GBM stem cells (GSCs). Moreover, SH2B3 high expression predicts worse survival of GBM patients. Targeting SH2B3 considerably impairs GBM cell proliferation, migration, and GSCs' self-renewal in vitro as well as xenograft tumors growth in vivo. Additionally, we provide evidence suggesting that STAT1 directly binds to the promoter of SH2B3 and activates SH2B3 expression in the transcriptional level. Functionally, SH2B3 facilitates GBM progression via physically interacting with gp130 and acting as an adaptor protein to transduce IL-6/gp130/STAT3 signaling. Together, our work firstly uncovers that the STAT1/SH2B3/gp130/STAT3 signaling axis plays critical roles in promoting GBM progression and provides insight into new prognosis marker and therapeutic target in GBM.
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The mortality rate of patients with glioma is increasing worldwide per annum. This is attributed to the poor disease prognosis, most notably for highgrade gliomas (grade III and IV), which does not improve the overall patient survival. The dysregulation of microRNA (miRNA/miR)1243p is found in a variety of tumors. However, the association between miR1243p expression and its target genes in glioma has not been thoroughly elucidated. The present study aimed to explore the possible effects of miR1243p and its proved target, Ras homology Growthrelated (RhoG), on the oncogenic events associated with glioblastoma multiforme (GBM) development. The data demonstrated an inverse association between miR1243p and RhoG expression levels during GBM progression in GBM tissues and cells. U87 and U251 cells were employed for the in vitro assays. Luciferase reporter assays revealed that miR1243p interacted with RhoG at the RhoG 3' untranslated region and inhibited RhoG expression in GBM cells. Functionally, enriched miR1243p repressed RhoG transcription and suppressed GBM cell proliferation and migration, promoting apoptosis and altering the expression or activity of the apoptosisrelated proteins of GBM cells. By contrast, the inhibition of miR1243p in GBM cells upregulated RhoG levels and promoted the proliferation of GBM cells. The knock down of RhoG expression by specific small interfering RNA sequences partially neutralized the effects induced by the miR1243p inhibitor. In conclusion, the present study demonstrated the crucial effects of miR1243p on the development and deterioration of GBM by targeting RhoG.
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Movimiento Celular , Glioblastoma/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Neoplásico/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Línea Celular Tumoral , Supervivencia Celular/genética , Glioblastoma/genética , Humanos , MicroARNs/genética , Proteínas de Neoplasias/genética , ARN Neoplásico/genética , Proteínas de Unión al GTP rho/genéticaRESUMEN
The LIM domain only 1 (LMO1) gene belongs to the LMO family of genes that encodes a group of transcriptional cofactors. This group of transcriptional cofactors regulates gene transcription by acting as a key "connector" or "scaffold" in transcription complexes. All LMOs, including LMO1, are important players in the process of tumorigenesis. Unique biological features of LMO1 distinct from other LMO members, such as its tissue-specific expression patterns, interacting proteins, and transcriptional targets, have been increasingly recognized. Studies indicated that LMO1 plays a critical oncogenic role in various types of cancers, including T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer. The molecular mechanisms underlying such functions of LMO1 have also been investigated, but they are currently far from being fully elucidated. Here, we focus on reviewing the current findings on the role of LMO1 in tumorigenesis, the mechanisms of its oncogenic action, and the mechanisms that drive its aberrant activation in cancers. We also briefly review its roles in the development process and non-cancer diseases. Finally, we discuss the remaining questions and future investigations required for promoting the translation of laboratory findings to clinical applications, including cancer diagnosis and treatment.
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Humanos , Masculino , Carcinogénesis/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Proteínas con Dominio LIM/genética , Factores de Transcripción/metabolismoRESUMEN
Objective:To explore the effects and mechanism of zedoary turmeric oil and its active components on the vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3 (STAT3), and mechanistic target of rapamycin (mTOR) in the ovarian cancer (OC). Method:Network pharmacology technology was employed to analyze the mechanism of Curcumae Rhizoma on OC. Bioinformatics was used to analyze the expression of VEGFA, STAT3, and mTOR in OC and the effect on the prognosis of OC to explore the feasibility of zedoary turmeric oil in regulating VEGFA, STAT3, and mTOR in OC.The xenograft tumor model of nude mice was established, and the effects of zedoary turmeric oil and its active components on VEGFA, STAT3, and mTOR in OC were observed by hematoxylin-eosin (HE) staining, real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR), Western blot, and immunohistochemistry (IHC). Result:Bioinformatics analysis and literature research showed that VEGFA, STAT3, and mTOR played a special regulatory role in the occurrence and development of OC, and were potential key targets for the proliferation of OC. Network pharmacology analysis revealed that Curcumae Rhizoma could regulate multiple disease targets of OC, and mediate VEGFA, STAT3, and mTOR in OC through these multiple targets. As demonstrated by HE staining, the tumor cells in the model group were densely arranged, with no erosion on the edge and no vesicles inside. Compared with the model group, the cell density in other treatment groups was reduced, and strip-shaped erosion on the edge and small empty vesicles were observed in the tumor tissue, especially in the zedoary turmeric oil group. According to the results of Real-time PCR and IHC, zedoary turmeric oil and its active components could inhibit the mRNA and protein expression of VEGFA, STAT3, and mTOR in the OC tissue (<italic>P</italic><0.05). Conclusion:Zedoary turmeric oil and its active components could reduce the expression of VEGFA, STAT3, and mTOR in tumor tissue of nude mice, and inhibited the proliferation of OC through VEGFA, STAT3, and mTOR.
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Objective:To investigate the ultrasonographic features and evolution of thyroid shrinking nodules in order to improve the differential diagnosis and management strategy and avoid unnecessary biopsy.Methods:A total of 245 patients with old bleeding of benign thyroid nodules diagnosed via fine needle aspiration cytology (FNAC) from May 2015 to July 2020 in the southern part of the Shanghai General Hospital Affiliated to the Medical College of Shanghai Jiaotong University, including 263 nodules. The sonographic parameters such as size, shape, aspect ratio, echo, edge, boundary, periphery, halo, calcification, posterior echo enhancement and posterior acoustic attenuation of nodules were analyzed retrospectively, and the ultrasonic appearances of nodules were classified; 41 nodules from 40 patients, who did ultrasound examinations more than twice and had both complete ultrasonographic data, were compared and then classified in order to explore the evolution rules of the nodules.Results:Two hundred and sixty-three thyroid shrinking nodules in 245 cases were classified into 4 types: "cystic wall shrinkage sign" type(71.48%, 188/263), "carcinoma-like" type (22.05%, 58/263), "inflammation-like" type(3.04%, 8/263) and "undefined atypical solid nodules" type(3.42%, 9/263). Of the 41 consecutive follow-up nodules, 37 cases showed obvious cystic wall shrinkage sign, and 7 of them developed into "carcinoma-like" type and 6 cases into "inflammation-like" type.Conclusions:The ultrasonographic appearance of thyroid shrinking nodules is a dynamic process, which can be divided into 4 types: "cystic wall shrinkage sign" , "carcinoma-like" , "inflammation-like" and "undefined atypical solid nodules" types. The "cystic wall shrinkage sign" type is typical and common. The "cystic wall shrinkage sign" type can develope into the "carcinoma-like" type or the "inflammation-like" type.
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BackgroundData regarding critical care for patients with severe COVID-19 are limited. We aimed to describe the clinical course, multi-strategy management, and respiratory support usage for the severe COVID-19 at the provincial level. MethodsUsing data from Sichuan Provincial Department of Health and the multicentre cohort study, all microbiologically confirmed COVID-19 patients in Sichuan who met the national severe criteria were included and followed-up from the day of inclusion (D1), until discharge, death, or the end of the study. FindingsOut of 539 COVID-19 patients, 81 severe cases (15.0%) were identified. The median (IQR) age was 50 (39-65) years, 37% were female, and 53.1% had chronic comorbidities. All severe cases were identified before requiring mechanical ventilation and treated in the intensive care units (ICUs), among whom 51 (63.0%) were treated in provisional ICUs and 77 patients (95.1%) were admitted by D1. On D1, 76 (93.8%) were administered by respiratory support, including 55 (67.9%) by conventional oxygen therapy (COT), 8 (9.9%) by high-flow nasal cannula (HFNC) and 13 (16.0%) by non-invasive ventilation (NIV). By D28, 53 (65.4%) were discharged, three (3.7%) were deceased, and 25 (30.9%) were still hospitalized. COT, administered to 95.1% of the patients, was the most commonly used respiratory support and met 62.7% of the respiratory support needed, followed by HFNC (19.3%), NIV ventilation (9.4%) and IV 8.5%. InterpretationThe multi-strategy management for severe COVID-19 patients including early identification and timely critical care may contribute to the low case-fatailty. Preparation of sufficient conventional oxygen equipment should be prioritized. Trial registration numberChiCTR2000029758.
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To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children. A total of 13 cases of ASPS diagnosed at Beijing Children's Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed. There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH. ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.