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BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has emerged as a promising alternative compared to conventional laparoscopic-assisted total gastrectomy (LATG) for treating gastric cancer (GC). However, evidence regarding the efficacy and safety of NOSES for GC surgery is limited. This study aimed to compare the safety and feasibility, in addition to postoperative complications of NOSES and LATG. AIM: To discuss the postoperative effects of two different surgical methods in patients with GC. METHODS: Dual circular staplers were used in Roux-en-Y digestive tract reconstruction for transvaginal specimen extraction LATG, and its outcomes were compared with LATG in a cohort of 51 GC patients with tumor size ≤ 5 cm. The study was conducted from May 2018 to September 2020, and patients were categorized into the NOSES group (n = 22) and LATG group (n = 29). Perioperative parameters were compared and analyzed, including patient and tumor characteristics, postoperative outcomes, and anastomosis-related complications, postoperative hospital stay, the length of abdominal incision, difference in tumor type, postoperative complications, and postoperative survival. RESULTS: Postoperative exhaust time, operation duration, mean postoperative hospital stay, length of abdominal incision, number of specific staplers used, and Brief Illness Perception Questionnaire score were significant in both groups (P < 0.01). In the NOSES group, the postoperative time to first flatus, mean postoperative hospital stay, and length of abdominal incision were significantly shorter than those in the LATG group. Patients in the NOSES group had faster postoperative recovery, and achieved abdominal minimally invasive incision that met aesthetic requirements. There were no significant differences in gender, age, tumor type, postoperative complications, and postoperative survival between the two groups. CONCLUSION: The application of dual circular staplers in Roux-en-Y digestive tract reconstruction combined with NOSES gastrectomy is safe and convenient. This approach offers better short-term outcomes compared to LATG, while long-term survival rates are comparable to those of conventional laparoscopic surgery.
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Medial epicondylitis, or golfer's elbow, is characterized by pain and tenderness at the tendon insertion points of the pronator teres and flexor carpi radialis. Conservative treatment is sufficient for most patients, whereas surgical treatment is the best choice for intractable medial epicondylitis. With open surgery or arthroscopic surgery, good clinical results have been reported. However, there is still no consensus on which surgical technique is more ideal. We describe our technique of arthroscopic medial bi-portal extra-articular debridement, which is a safe and effective technique that allows more accurate debridement and maximum protection of the ulnar nerve while reducing surgical scars, relieving postoperative pain, reducing the probability of elbow infection and ankylosis, and shortening the recovery time.
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Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopénica Idiopática/complicaciones , Calidad de Vida , Estudios Retrospectivos , Estudios Prospectivos , Hemorragia/diagnóstico , Trombocitopenia/complicacionesRESUMEN
In recent years, natural orifice specimen extraction surgery (NOSES), a novel minimally invasive surgical technique, has become a focus in the surgical field, and has been initially applied in gastric surgery in many national medical centers worldwide. In addition, this new surgical technique was launched in major hospitals in China. With an increasing number of patients who have accepted this new surgical technique, NOSES has provided new prospects for the treatment of gastric cancer (GC), which may achieve a better outcome for both patients and surgeons. More and more experts and scholars from different countries and regions are currently paying close attention to NOSES for the treatment of GC. However, there are only a few reports of its use in GC. This review focuses on the research progress in NOSES for radical gastrectomy in recent years. We also discuss the challenges and prospects of NOSES in clinical practice.
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Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.
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Púrpura Trombocitopénica Idiopática , Adulto , Hemorragia Cerebral/complicaciones , Escala de Coma de Glasgow , Humanos , Hemorragias Intracraneales/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/epidemiología , Curva ROCRESUMEN
Objectives: To explore the feasibility of predicting overall survival (OS) of patients with midline glioma using multi-parameter magnetic resonance imaging (MRI) features. Methods: Data of 84 patients with midline gliomas were retrospectively collected, including 40 patients with OS > 12 months (28 cases were adults, 14 cases were H3 K27M-mutation) and 44 patients with OS < 12 months (29 cases were adults, 31 cases were H3 K27M-mutation). Features were extracted from the largest slice of tumors, which were manually segmented on T2-weighted (T2w), T2 fluid-attenuated inversion recovery (T2 FLAIR), and contrast-enhanced T1-weighted (T1c) images. Data were randomly divided into training (70%) and test cohorts (30%) and normalized and standardized using Z-scores. Feature dimensionality reduction was performed using the variance method and maximum relevance and minimum redundancy (mRMR) algorithm. We used the logistic regression algorithm to construct three models for T2w, T2 FLAIR, and T1c images as well as one combined model. The test cohort was used to evaluate the models, and receiver operating characteristic (ROC) curves, areas under the curve (AUCs), sensitivity, specificity, and accuracy were calculated. The nomogram of the combined model was built and evaluated using a calibration curve. Decision curve analysis (DCA) was used to evaluate the clinical application value of the four models. Results: A total of 1,316 features were extracted from T2w, T2 FLAIR, and T1c images, respectively. And then the best non-redundant features were selected from the extracted features using the variance method and mRMR. Finally, five features were extracted each from T2w, T2 FLAIR, and T1c images, and 12 features were extracted for the combined model. Four models were established using the optimal features. In the test cohort, the combined model performed the best out of all models. The AUCs of the T2w, T2 FLAIR, T1c, and combined models were 0.73, 0.78, 0.74, and 0.87, respectively, and accuracies were 0.72, 0.76, 0.72, and 0.84, respectively. The ROC curves and DCA showed that the combined model had the highest efficiency and most favorable clinical benefits. Conclusion: The combined radiomics model based on multi-parameter MRI features provided a reliable non-invasive method for the prognostic prediction of midline gliomas.
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The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.
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Antineoplásicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Rituximab/uso terapéutico , Tretinoina/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Antineoplásicos/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab/administración & dosificación , Prevención Secundaria , Tretinoina/administración & dosificaciónRESUMEN
BACKGROUND: We compared short-term perioperative outcomes after single-incision plus one-port laparoscopic gastrectomy (SILG+1) and conventional multi-port laparoscopy-assisted gastrectomy (C-LAG) for gastric cancer. METHODS: The work was conducted between August 2017 and October 2019. A total of 90 patients with early or advanced gastric cancer were retrospectively analyzed: 43 patients of which underwent SILG+1, and 47 of which underwent C-LAG, respectively. These were divided into two groups: the total gastrectomy group (SILT+1 and C-LATG) and the distal gastrectomy group (SILD + 1 and C-LADG). The demographics, tumor characteristics, postoperative outcomes, and short-term complications of all enrolled patients were summarized and statistically analyzed. RESULTS: The mean incision length in SILT+1 group was 5.40 cm shorter than that in C-LATG group (3.15 ± 0.43 vs. 8.55 ± 2.72, P < 0.001). This comparison between the SILD + 1 and the C-LADG group produced comparable results. The SILT+1 group underwent a 56.32 min longer operation than the C-LATG group (273.03 ± 66.80 vs. 216.71 ± 82.61, P = 0.0205). SILG+1 group had better postoperative visual analog scale (VAS) and cosmetic score than those of the C-LATG group (P < 0.05). There were no significant differences in preoperative demographics or 30-day postoperative complication rates between the SILG+1 and C-LAG groups. Tumor-related index, including mass size, histological type, number of retrieved lymph nodes, pathological tumor-node-metastasis (TNM) stage, and proximal and distal edges were all equivalent between the SILG+1 and the C-LAG group. CONCLUSIONS: This retrospective study demonstrates the safety and feasibility of SILG+1 with D1+ or D2 lymphadenectomy for the treatment of early and advanced gastric cancers, compared with C-LAG.
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Laparoscopía , Neoplasias Gástricas , Herida Quirúrgica , Gastrectomía/métodos , Humanos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Neoplasias Gástricas/patología , Herida Quirúrgica/complicaciones , Resultado del TratamientoRESUMEN
Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.
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Hemorragias Intracraneales/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Femenino , Humanos , Hemorragias Intracraneales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Resultado del TratamientoRESUMEN
Infection is one of the primary causes of death from immune thrombocytopenia (ITP), and the lungs are the most common site of infection. We identified the factors associated with hospitalization for community-acquired pneumonia (CAP) in nonsplenectomized adults with ITP and established the [corrected] (ACPA) prediction model to predict the incidence of hospitalization for CAP. This was a retrospective study of nonsplenectomized adult patients with ITP from 10 large medical centers in China. The derivation cohort included 145 ITP inpatients with CAP and 1360 inpatients without CAP from 5 medical centers, and the validation cohort included the remaining 63 ITP inpatients with CAP and 526 inpatients without CAP from the other 5 centers. The 4-item ACPA model, which included age, Charlson Comorbidity Index score, initial platelet count, and initial absolute lymphocyte count, was established by multivariable analysis of the derivation cohort. Internal and external validation were conducted to assess the performance of the model. The ACPA model had an area under the curve of 0.853 (95% confidence interval [CI], 0.818-0.889) in the derivation cohort and 0.862 (95% CI, 0.807-0.916) in the validation cohort, which indicated the good discrimination power of the model. Calibration plots showed high agreement between the estimated and observed probabilities. Decision curve analysis indicated that ITP patients could benefit from the clinical application of the ACPA model. To summarize, the ACPA model was developed and validated to predict the occurrence of hospitalization for CAP, which might help identify ITP patients with a high risk of hospitalization for CAP.
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Neumonía , Púrpura Trombocitopénica Idiopática , Adulto , China , Hospitalización , Humanos , Neumonía/epidemiología , Púrpura Trombocitopénica Idiopática/epidemiología , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Bases de Datos Genéticas , Haplotipos , Herencia Multifactorial , Oryza/genética , Minería de Datos , FenotipoRESUMEN
OBJECTIVE: To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD). METHODS: The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively. RESULTS: Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (Pï¼0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1ß and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (Pï¼0.01ï¼, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (Pï¼0.05ï¼, no significant difference of the rest cytokines was found between iMCD and the control group. CONCLUSION: IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 ãIL-21ãIL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.
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Enfermedad de Castleman , Citocinas , Humanos , Interleucina-12 , Interleucina-1beta , PlasmaRESUMEN
Aryl hydrocarbon receptor nuclear translocator protein 2 (ARNT2), a member of the basic helix-loop-helix superfamily of transcription factors, may serve a vital role in neuronal survival and cell proliferation via formation of heterodimers with hypoxia-inducible factor-1α. Previous studies indicated that ARNT2 levels were elevated in the brains of ischemic rats; however, the involvement of ARNT2 in post-stroke depression (PSD) rats is not well understood. Therefore, the present study aimed to investigate the levels of ARNT2 in the hippocampi of PSD rats, and to clarify the potential association between ARNT2 and behavioral performance. A PSD rat model was established by middle cerebral artery occlusion (MCAO) followed by a 4-week chronic unpredictable mild stress (CUMS) regimen. A sucrose preference test and open field test (OFT) were conducted, and body weight was measured. In addition, reverse transcription-polymerase chain reaction and immunohistochemistry were performed to measure ARNT expression. Results indicated that MCAO+CUMS rats had lower weight gain, consumed less sucrose and moved less compared with controls. Furthermore, the mRNA and protein levels of ARNT in MCAO+CUMS rats were increased compared with in controls. The sucrose preference index and horizontal movement distance in the OFT were positively correlated with ARNT mRNA level. Thus, from these findings it was suggested that ARNT2 may be positively associated with improvement of cognitive impairment, and therefore may be a potential target in PSD treatment.
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OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43â¶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31â¶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 3î49 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION: Bone lymphoma is usually concealed onsetï¼an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
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Neoplasias Óseas , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios RetrospectivosRESUMEN
Depression is a condition with a complex etiological pattern, whose effective treatments are highly limited. MicroRNAs (miRNAs) have been investigated in intensive studies owing to their involvement in pathophysiology of mood disorders. The current study aimed to elucidate the role of miR-301b in hippocampus in mouse models of depressive-like behavior. Microarray-based prediction identified the differentially expressed gene neuronal pentraxin II (NPTX2) related to mental depression. Next, the putative miR-301b binding sites on the 3'UTR of NPTX2 were verified. Then the effect of miR-301b on cognitive function of mice with depressive-like behavior was analyzed using the Morris water maze test. In addition, the regulation of miR-301b to NPTX2 and activation of NF-κB signaling pathway was assessed. Following that, the microglia activation and inflammation in hippocampus were evaluated, with the expressions of inflammatory factors being examined. At last, microglia were flow cytometrically sorted and the inflammatory reaction was also assessed in vitro. The obtained findings revealed that miR-301b targeted and negatively regulated NPTX2. Moreover, overexpressed miR-301b activated the NF-κB signaling pathway, as reflected by increasing protein expressions of p-NF-κB. Upregulated miR-301b accelerated cognitive impairment in mice with depressive-like behavior. In addition, overexpression of miR-301b activated microglia and stimulated inflammation in hippocampus, accompanied by enhanced release of tumor necrosis factor-α (TNF-α), interleukin-Iß (IL-Iß) and cyclooxygenase-2(COX-2). Taken together, the evidence provided by the current study indicated that overexpression of miR-301b augmented hippocampal microglia activation, thus exacerbating cognitive impairment and inflammation in mice with depressive-like behavior by activating the NF-κB signaling pathway.
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Disfunción Cognitiva/metabolismo , Trastorno Depresivo/metabolismo , Hipocampo/metabolismo , MicroARNs/metabolismo , Microglía/metabolismo , FN-kappa B/metabolismo , Animales , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Disfunción Cognitiva/genética , Ciclooxigenasa 2/metabolismo , Trastorno Depresivo/genética , Femenino , Hipocampo/inmunología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Ratones , Ratones Endogámicos ICR , MicroARNs/genética , Microglía/inmunología , FN-kappa B/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Transducción de Señal/genética , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: The therapeutic planning varies for different grades of choroid plexus tumours (CPTs). The aim of this study was to define the similarities and distinctions among MRIs for different grades of CPTs, providing more guidance for clinical decisions. METHODS: We reviewed the MRI findings in 35 patients with CPT verified by surgical pathology, including 18 choroid plexus papillomas (CPPs, grade I), 11 atypical choroid plexus papillomas (aCPPs, grade II), and 6 choroid plexus carcinomas (CPCs, grade III). Nonparametric testing based on ranks was performed to evaluate the association of pathological grade with MRI findings. RESULTS: Among the 35 CPTs, 29 were located in the ventricular system. The tumours were generally slightly hypo- or isointense on T1WI, slightly hyper- or isointense on T2WI, and moderately or strongly enhanced in post-contrast imaging. Twenty cases were accompanied by hydrocephalus. The median tumour longest diameters of CPPs, aCPPs, and CPCs were 28.6, 44.6, and 60.6 mm, respectively. Four cases were purely cystic, 6 were papillary, 10 were lobulated, and 2 were irregular. Three cases had necrosis. The median oedema diameters of CPPs, aCPPs, and CPCs were 0, 0, and 24.1 mm, respectively. The grades of CPTs were statistically associated with tumour longest diameter (rs = 0.68, P < 0.001), internal morphology (χ2 = 10.32, P = 0.016), necrosis (Z = 2.27, P = 0.023), and oedema diameter (rs = 0.72, P < 0.001). CONCLUSION: CPTs typically appeared as intraventricular papillary or lobulated lesions, often accompanied by hydrocephalus. Larger tumour, irregular or fuzzy internal morphology, presentation of necrosis and wide-ranging peritumoural oedema might increase the likelihood of malignancy.
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Neoplasias del Plexo Coroideo/diagnóstico por imagen , Neoplasias del Plexo Coroideo/patología , Imagen por Resonancia Magnética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Adulto JovenRESUMEN
BACKGROUND: Atypical protein kinase C-ι (aPKC-ι) is an oncogenic factor, and required for the epithelial-mesenchymal transition (EMT) of different types of cancer. Our study aimed to investigate the role of aPKC-ι in the EMT, migration and invasion of colorectal cancer (CRC) cells. METHODS: Expression of aPKC-ι was evaluated in CRC cell lines treated with TGF-ß1 using qPCR and western blot. After aPKC-ι was knocked down using shRNA, migration and invasion abilities of CRC cell lines were evaluated by wound healing assay and transwell assay, respectively. Activation status of downstream signaling factors of aPKC-ι, including Rac1, JNK, STAT3 and ß-catenin, was measured using western blot. Furthermore, auranofin, an aPKC-ι inhibitor, was used to treat CRC cell lines to investigate its possible inhibition on the EMT of CRC cell lines, as well as on the expression of aPKC-ι and its downstream signaling factors. RESULTS: TGF-ß1 induced the expression of aPKC-ι in CRC cells, and knockdown on aPKC-ι inhibited the TGF-ß1-induced EMT, migration and invasion of CRC cells. Interestingly, Rac1 GTPase level was decreased when aPKC-ι was knocked down, and overexpression of Rac1G12V rescued the cell EMT, migration and invasion in CRC cells as inhibited by sh-aPKC-ι. Moreover, knockdown on aPKC-ι suppressed the phosphorylation of JNK and STAT3, and nuclear translocation of ß-catenin. The aPKC- ι inhibitor, Auranofin, showed similar inhibitory effects as aPKC-ι knockdown. CONCLUSION: Knockdown on aPKC-ι inhibited the EMT, migration and invasion of CRC cells through suppressing of Rac1-JNK pathway. Those findings indicate that aPKC-ι may serve as a novel therapeutic target for CRC.
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Movimiento Celular/fisiología , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/fisiología , Isoenzimas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Proteína Quinasa C/metabolismo , Proteína de Unión al GTP rac1/metabolismo , Línea Celular Tumoral , Humanos , Invasividad Neoplásica/fisiopatologíaRESUMEN
Depression represents a condition characterized by cognitive deficits and neural dysfunction and has recently been correlated with microRNAs (miRs) and their respective target genes. The present study was conducted with the goal of investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2 in an attempt to evaluate their roles in the occurrence and progression of cognitive impairment and neural function in mice with chronic unpredictable mild stress (CUMS)-induced depression through regulation of the TGF-ß1 signal transduction pathway. Verification of the targeting relationship between miR-192-5p and Fbln2 was provided in the form of initial bioinformatics prediction, followed by a further verification in the form of a dual-luciferase reporter gene assay. Normal mice and models induced by CUMS were assigned into various groups, whereas mimics, inhibitors, and small interfering RNA were introduced to validate the regulatory mechanism by which miR-192-5p regulates Fbln2 depression. Novel object recognition, tail suspension testing, and Morris water maze were all employed 28 d after transfection. Hippocampal electrophysiological recordings, Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry were performed to further evaluate cognitive function and neuron regeneration. CUMS-induced depression was determined to represent a predisposing factor for cognitive impairment and damage to neural function in mice, highlighted by novel object recognition, learning and memory abilities, population spike amplitude, synaptic transmission, cAMP levels, neuronal regeneration, and increased behavioral changes that resemble depression. Furthermore, increased Fbln2 expression, an activated TGF-ß1 signaling pathway, and decreased expression of miR-192-5p, synaptophysin, brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, and calmodulin-dependent protein kinase II were noted. Up-regulated miR-192-5p targeting Fbln2 acts to alleviate CUMS-induced depression by inhibiting the TGF-ß1 signaling pathway, resulting in the enhanced cognitive function in novel object recognition, learning and memory ability, population spike amplitude, synaptic transmission, neuron regeneration, and alleviation of behavioral symptoms. The central findings of the present study indicate that up-regulated levels of miR-192-5p expression act to suppress activation of the TGF-ß1 signaling pathway by means of binding to Fbln2, thereby ameliorating cognitive impairment and strengthening neural function in a mouse model of depression.-Tang, C.-Z., Yang, J.-T., Liu, Q.-H., Wang, Y.-R., Wang, W.-S. Up-regulated miR-192-5p expression rescues cognitive impairment and restores neural function in mice with depression via the Fbln2-mediated TGF-ß1 signaling pathway.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Disfunción Cognitiva/prevención & control , Depresión/complicaciones , Modelos Animales de Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , MicroARNs/genética , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Conducta Animal , Proteínas de Unión al Calcio/genética , Proliferación Celular , Disfunción Cognitiva/etiología , Depresión/fisiopatología , Proteínas de la Matriz Extracelular/genética , Regulación de la Expresión Génica , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Factor de Crecimiento Transformador beta1/genética , Regulación hacia ArribaRESUMEN
OBJECTIVE: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human gastric cancer MKN45 cells and its mechanism and provide experimental basis for the prevention and treatment of gastric cancer with Traditional Chinese Medicine (TCM). METHODS: MKN45 cells were pre-treated with DHM (0,10,20,30,40,50 µmol/L) for 24 and 48 hours respectively. Cell viability treated with different concentrations of DHM was detected by Cell Counting kit (CCK-8) assay, cell migration was measured by wound healing assay, and cell invasion was tested by Transwell assay. Cells were pre-treated with DHM or co-treated with c-Jun N-terminal kinase (JNK) pathway inhibitor SP600125, then, the levels of migration- and invasion-related proteins were tested by Western blot. RESULTS: DHM concentration-dependently inhibited cell migration and invasion and downregulated matrix metalloprotein -2 (MMP-2) and phosphorylated JNK (pJNK) expression in MKN45 cells, followed by upregulation of E-cadherin and downregulation of Vimentin. Co-treatment with DHM and JNK inhibitor SP600125 further suppressed MMP-2 expression and cell invasion in MKN45 cells, suggesting that DHM inhibited MKN45 cells metastasis through JNK/MMP-2 pathway. CONCLUSION: DHM can inhibit cell migration and invasion in human gastric cancer MKN45 cells through downregulating MMP-2 expression via JNK signaling pathway and reverse epithelial-mesenchymal transition (EMT), implying that DHM could have the potential to serve as an anti-metastatic agent for treating gastric cancer.