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1.
Eur J Radiol ; 181: 111763, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39341168

RESUMEN

PURPOSE: To develop a CT radiomics model to predict pathological complete response (pCR) of advanced esophageal squamous cell carcinoma (ESCC) toneoadjuvant chemotherapy using paclitaxel and cisplatin. MATERIALS AND METHODS: 326 consecutive patients with advanced ESCC from two hospitals undergoing baseline contrast-enhanced CT followed by neoadjuvant chemotherapy using paclitaxel and cisplatin were enrolled, including 115 patients achieving pCR and 211 patients without pCR. Of the 271 cases from 1st hospital, 188 and 83 cases were randomly allocated to the training and test cohorts, respectively. The 55 patients from a second hospital were assigned as an external validation cohort. Region of interest was segmented on the baseline thoracic contrast-enhanced CT. Useful radiomics features were generated by dimension reduction using least absolute shrinkage and selection operator. The optimal radiomics features were chosen using support vector machine (SVM). Discriminating performance was assessed with area under the receiver operating characteristic curve (ROC) and F-1score. The calibration curves and Brier score were used to evaluate the predictive accuracy. RESULTS: Eight radiomics features were selected to create radiomics models related to pCR of advanced ESCC (P-values < 0.01 for both the training and test cohorts). SVM model showed the best performance (AUCs = 0.929, 0.868 and 0.866, F-1scores = 0.857, 0.847 and 0.737 in the training, test and external validation cohorts, respectively). The calibration curves and Brier scores indicated goodness-of-fit and its great predictive accuracy. CONCLUSION: CT radiomics models could well help predict pCR of advanced ESCC, and SVM model could be a suitable predictive model.

2.
J Ethnopharmacol ; 331: 118306, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38723920

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Invigorating blood circulation to remove blood stasis is a primary strategy in TCM for treating vascular dementia (VaD). Danggui-Shaoyao San (DSS), as a traditional prescription for neuroprotective activity, has been proved to be effective in VaD treatment. However, its precise molecular mechanisms remain incompletely understood. AIM OF THE STUDY: The specific mechanism underlying the therapeutic effects of DSS on VaD was explored by employing network pharmacology as well as in vivo and in viro experiment validation. MATERIALS AND METHODS: We downloaded components of DSS from the BATMAN-TCM database for target prediction. The intersection between the components of DSS and targets, PPI network, as well as GO and KEGG enrichment analysis were then performed. Subsequently, the potential mechanism of DSS predicted by network pharmacology was assessed and validated through VaD rat model induced by 2VO operation and CoCl2-treated PC12 cells. Briefly, the DSS extract were first quantified by HPLC. Secondly, the effect of DSS on VaD was studied using MWM test, HE staining and TUNEL assay. Finally, the molecular mechanism of DSS against VaD was validated by Western blot and RT-QPCR experiments. RESULTS: Through network analysis, 137 active ingredients were obtained from DSS, and 67 potential targets associated with DSS and VaD were identified. GO and KEGG analysis indicated that the action of DSS on VaD primarily involves hypoxic terms and HIF-1 pathway. In vivo validation, cognitive impairment and neuron mortality were markedly ameliorated by DSS. Additionally, DSS significantly reduced the expression of proteins related to synaptic plasticity and neuron apoptosis including PSD-95, SYP, Caspase-3 and BCL-2. Mechanistically, we confirmed DSS positively modulated the expression of HIF-1α and its downstream proteins including EPO, p-EPOR, STAT5, EPOR, and AKT1 in the hippocampus of VaD rats as well as CoCl2-induced PC12 cells. HIF-1 inhibitor YC-1 significantly diminished the protection of DSS on CoCl2-induced PC12 cell damage, with decreased HIF-1α, EPO, EPOR expression. CONCLUSION: Our results initially demonstrated DSS could exert neuroprotective effects in VaD. The pharmacological mechanism of DSS may be related to its positive regulation on HIF-1α/EPO pathway.


Asunto(s)
Disfunción Cognitiva , Demencia Vascular , Medicamentos Herbarios Chinos , Eritropoyetina , Subunidad alfa del Factor 1 Inducible por Hipoxia , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/metabolismo , Ratas , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células PC12 , Masculino , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Fármacos Neuroprotectores/farmacología , Eritropoyetina/farmacología , Apoptosis/efectos de los fármacos , Farmacología en Red , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Cobalto
3.
Eur J Radiol ; 175: 111479, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663124

RESUMEN

PURPOSE: To construct and validate CT radiomics model based on the peritumoral adipose region of gastric adenocarcinoma to preoperatively predict lymph node metastasis (LNM). METHODS AND METHODS: 293 consecutive gastric adenocarcinoma patients receiving radical gastrectomy with lymph node dissection in two medical institutions were stratified into a development set (from Institution A, n = 237), and an external validation set (from Institution B, n = 56). Volume of interest of peritumoral adipose region was segmented on preoperative portal-phase CT images. The least absolute shrinkage and selection operator method and stepwise logistic regression were used to select features and build radiomics models. Manual classification was performed according to routine CT characteristics. A classifier incorporating the radiomics score and CT characteristics was developed for predicting LNM. Area under the receiver operating characteristic curve (AUC) was used to show discrimination between tumors with and without LNM, and the calibration curves and Brier score were used to evaluate the predictive accuracy. Violin plots were used to show the distribution of radiomics score. RESULTS: AUC values of radiomics model to predict LNM were 0.938, 0.905, and 0.872 in the training, internal test, and external validation sets, respectively, higher than that of manual classification (0.674, all P values < 0.01). The radiomics score of the positive LNM group were higher than that of the negative group in all sets (both P-values < 0.001). The classifier showed no improved predictive power compared with the radiomics signature alone with AUC values of 0.916 and 0.872 in the development and external validation sets, respectively. Multivariate analysis showed that radiomics score was an independent predictor. CONCLUSIONS: Radiomics model based on peritumoral adipose region could be a useful approach for preoperative LNM prediction in gastric adenocarcinoma.


Asunto(s)
Adenocarcinoma , Tejido Adiposo , Metástasis Linfática , Neoplasias Gástricas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Masculino , Femenino , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Metástasis Linfática/diagnóstico por imagen , Anciano , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Valor Predictivo de las Pruebas , Adulto , Gastrectomía , Estudios Retrospectivos , Reproducibilidad de los Resultados , Escisión del Ganglio Linfático , Radiómica
4.
Herald of Medicine ; (12): 255-261, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1023707

RESUMEN

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

5.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1023988

RESUMEN

Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.

6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031100

RESUMEN

【Objective】 To analyze the associations between different types of video screen time and psychological behaviors of preschool children, in order to provide evidence for promoting the development of children′s mental health. 【Methods】 From February to March 2023, a total of 1 361 parents of children aged 3 - 6 years from 6 kindergartens of Lanzhou were surveyed by cluster sampling method.Parents were surveyed to obtain information about the video use, and the children′s Strengths and Difficulties questionnaire (parent version) was used to assess children′s psychological and behavioral problems. 【Results】 The rate of daily screen time exceeding standard was 36.96% (503/1 361).The screen time was mainly spent in watching TV cartoons, followed by educational APP.The detection rate of abnormal total difficulty score was 11.61% (158/1 361), and the abnormalities of peer communication (32.26%) and prosocial behavior (12.34%) were the most prominent.After adjusting for related factors by multiple Logistic regression analysis, total screen time≥2h/d (OR=1.802) was found to be a risk factor for abnormal total difficulty score; watching TV cartoons≥2h/d was a risk factor for abnormal total difficulty score (OR=2.409) and peer communication (OR=2.222); playing games≥1h/d was a risk factor for abnormal total difficulty score, emotional symptoms, conduct problems, hyperactive behavior, and abnormalities of peer communication, the differences were all statistically significant (P<0.05).However, educational APP screen time<1h/d was a protective factor for abnormal total difficulty score(OR=0.615) and prosocial behavior (OR=0.549), but educational APP screen time≥2h/d was a risk factor for conduct problems (OR=2.302), the differences were all statistically significant (P<0.05). 【Conclusions】 The screen time of preschool children in Lanzhou cannot be ignored, and there is a significant correlation between overuse and children′s psychological and behavioral problems.Parents and schools should attach importance to the parent-child and peer interaction of preschool children and strengthen the intervention of preschool children′s video behavior.

7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1031621

RESUMEN

【Objective】 To compare the risk of generalization in patients with ocular myasthenia gravis (OMG) receiving or not receiving immunosuppressive treatment. 【Methods】 The data of patients with OMG registered in Tangdu Hospital of Air Force Military Medical University from January 1, 2015 to May 1, 2019 were reviewed; the patients were divided into treatment group and control group according to whether they had received immunosuppressive treatment. The multivariate Cox proportional hazards regression model analysis was used to compare the risk of generalization between the two groups of patients within 2 years of onset. Sensitivity analysis was used to evaluate the duration of immunosuppressive treatment and the risk of generalization under different immunotherapy regimens. By using stratified analysis, the consistency of the main results across different levels of subgroup factors was evaluated. 【Results】 A total of 702 OMG patients were collected. Of them 367 patients (52.3%) were included in the treatment group, with an average onset age of (50.54±15.1) years, and 159 (43.3%) being female. Another 335 patients (47.7%) were included in the control group, with an average age of (49.1±14.6) years, and 159 ones (47.5%) were female. A total of 28 cases (7.7%) in the treatment group and 106 cases (31.6%) in the control group developed generalization during the observation period. After multivariate-adjusted Cox model analysis, patients who had received immunosuppressive treatment had a significantly lower risk of generalization compared with the control group (HR=0.24; 95% CI: 0.15-0.37; P<0.001). Sensitivity analysis found that the longer the duration of immunosuppression, the lower the risk of generalization (HR=0.88; 95% CI: 0.85-0.91; P<0.001). Stratified analysis showed that immunosuppressive therapy reduced the risk of generalization in different subgroups of patients. 【Conclusion】 Early immunosuppressive treatment can significantly reduce the risk of generalization in patients with OMG.

8.
Workplace Health Saf ; 71(6): 282-295, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36988052

RESUMEN

BACKGROUND: Female nurses are a high-risk group for pelvic floor dysfunction (PFD). Predictors of female nurses' PFD among work-related factors are not well known. The aim of this study was to investigate the prevalence of PFD and its association with workplace conditions among female nurses in China. METHODS: An online cross-sectional survey was conducted in May 2021. A sample of 380 registered nurses working in six tertiary hospitals in Nanjing, China participated. Data on individual characteristics, work-related factors, the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 were used. FINDINGS: The overall prevalence of PFD among nurses was 83.9%, with 43.9% of participants experiencing pelvic organ prolapse, 66.6% experiencing anorectal dysfunction and 60.5% experiencing lower urinary tract symptoms. In terms of work-related factors, PFD was associated with heavy lifting, pushing, and carrying at work, delayed toileting at work and fluid intake. Female nurses with PFD reported lower quality of life (QoL) relative to nurses without PFD. CONCLUSIONS/APPLICATION TO PRACTICE: Our findings provide initial insights into workplace conditions that promote PFD among female nurses. Occupational health nurses should consider providing educational information for female workers who are potentially at risk for PFD and consider integrating screening of PFD into practice.


Asunto(s)
Trastornos del Suelo Pélvico , Prolapso de Órgano Pélvico , Femenino , Humanos , Trastornos del Suelo Pélvico/epidemiología , Trastornos del Suelo Pélvico/complicaciones , Calidad de Vida , Diafragma Pélvico , Estudios Transversales , Prolapso de Órgano Pélvico/complicaciones , Prolapso de Órgano Pélvico/epidemiología , Encuestas y Cuestionarios
9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970702

RESUMEN

Objective: To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in the alteration of tight junction protein expression in choroid plexus epithelial cells created by lanthanum-activated matrix metalloproteinase 9 (MMP9) . Methods: In October 2020, immortalized rat choroid plexus epithelial cell line (Z310) cells were used as the blood-cerebrospinal fluid barrier in vitro, and were divided into control group and 0.125, 0.25, 0.5 mmol/L lanthanum chloride (LaCl(3)) treatment group. After treating Z310 cells with different concentrations of LaCl(3) for 24 hours, the morphological changes of Z310 cells were observed under inverted microscope, the protein expression levels of MMP9, occludin and zonula occludens-1 (ZO-1) were observed by cellular immunofluorescence method, and the protein expression levels of MMP9, tissue inhibitors of metalloproteinase1 (TIMP1) , occludin, ZO-1 and Nrf2 were detected by Western blotting. The level of reactive oxygen species (ROS) in cells was detected by flow cytometry. Results: Compared with the control group, Z310 cells in the LaCl(3) treatment group were smaller in size, with fewer intercellular junctions, and more dead cells and cell fragments. The expression level of MMP9 protein in cells treated with 0.25 and 0.5 mmol/L LaCl(3) was significantly higher than that in the control group (P<0.05) , and the expression level of TIMP1 and tight junction proteins occudin and ZO-1 was significantly lower than that in the control group (P<0.05) . Compared with the control group, the ROS production level in the 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly increased (P<0.05) , and the Nrf2 protein expression level in the 0.125, 0.25, 0.5 mmol/L LaCl(3) treatment group was significantly decreased (P<0.05) . Conclusion: Lanthanum may increase the level of ROS in cells by down regulating the expression of Nrf2, thus activating MMP9 to reduce the expression level of intercellular tight junction proteins occludin and ZO-1.


Asunto(s)
Ratas , Animales , Metaloproteinasa 9 de la Matriz/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Ocludina/farmacología , Plexo Coroideo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Lantano/farmacología , Células Epiteliales , Proteína de la Zonula Occludens-1/metabolismo , Fosfoproteínas/farmacología
10.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-993373

RESUMEN

Hypersplenism is an important complication of cirrhotic portal hypertension, and splenectomy is an important means to treat hypersplenism in cirrhosis. It is realized that hypersplenism played a pathological role in the course of cirrhosis. This article analyzes and compares the changes in the condition of patients with cirrhosis between splenectomy with and without hyperfunction, and comprehensively discusses the pathological role and mechanism of hypersplenism in the course of cirrhosis, in order to strengthen the clinical prevention and treatment of hypersplenism in cirrhosis and to better improve the condition and prognosis of patients with cirrhosis.

11.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-487739

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has caused over 6 million death and 460 million reported cases globally. More effective antiviral medications are needed to curb the continued spread of this disease. The infection by SARS-COV-2 virus is initiated via the interaction between the receptor binding domain (RBD) of the viral glycoprotein Spike (S protein) and the N-term peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2) expressed on host cell membrane. ACE2 forms protein homodimer primarily through its ferredoxin-like fold domain (aka. Neck-domain). We investigated whether the dimerization of ACE2 receptor plays a role in SARS-COV-2 virus infection. We report here that the ACE2 receptor dimerization enhances the recognition of SARS-COV-2 S protein. A 43 amino acid peptide based on the N-term of Neck-domain could block the ACE2 dimerization and the interaction between RBD and ACE2, and mitigate the SARS-COV-2/host cell interaction. Our study illustrated a new route to develop potential therapeutics for the prevention and treatment of SARS-COV-2 viral infection.

12.
International Journal of Surgery ; (12): 351-355, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-930023

RESUMEN

Colorectal cancer is a common tumor of the digestive system with a high degree of malignancy. Most patients are in the advanced stages of the disease when they develop symptoms. Although the detection rate of traditional screening methods is improving with advances in imaging and the popularity of colonoscopy, the diagnosis of early, asymptomatic colon cancer is still unsatisfactory. Therefore, it is particularly important to further study the occurrence and development mechanism of colorectal cancer and obtain new ideas for the diagnosis and treatment.? In recent years, with the deepening of epigenetics research, the role of DNA methylation in the pathogenesis of colorectal cancer has gradually attracted attention. This paper will review the research progress of DNA methylation in colorectal cancer′s diagnosis and treatment.

13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-939623

RESUMEN

Microfluidics is the science and technology to manipulate small amounts of fluids in micro/nano-scale space. Multiple modules could be integrated into microfluidic device, and due to its advantages of microminiaturization and controllability, microfluidics has drawn extensive attention since its birth. In this paper, the literature data related to microfluidics research from January 1, 2006 to December 31, 2021 were obtained from Web of Science Core Collection database. CiteSpace 5.8.R3 software was used for bibliometrics analysis, so as to explore the research progress and development trends of microfluidics research at home and abroad. Based on the analysis of 50 129 articles, it could be seen that microfluidics was a hot topic of global concern, and the United States had a certain degree of authority in this field. Massachusetts Institute of Technology and Harvard University not only had a high number of publications, but also had strong influence and extensive cooperation network. Combined with ultrasonic, surface modification and sensor technology, researchers constructed paper-based microfluidic, droplet microfluidic and digital microfluidic platforms, which were applied in the field of immediate diagnosis, nucleic acid and circulating tumor cell analysis of in vitro diagnosis and organ-on-a-chip. China was one of the countries with a high level of research in the field of microfluidics, while the industrialization of high-end products needed to be improved. As people's demand for disease risk prediction and health management increased, promoting microfluidic technological innovation and achievement transformation is of great significance to safeguard people's life and health.


Asunto(s)
Humanos , China , Técnicas Analíticas Microfluídicas , Microfluídica , Análisis de Secuencia por Matrices de Oligonucleótidos
14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-958579

RESUMEN

In vitro diagnosis (IVD) is an important source of clinical diagnostic information, and provides an important decision basis for disease prevention, diagnosis and treatment. IVD is a necessary tool for promoting graded diagnosis and treatment, realizing precision medicine, constructing a "Healthy China" and responding to major public health emergencies. Combining the great progress made in the development of in vitro diagnostics in China and the shortcomings and weaknesses faced by it, this article analyzed the demand for IVD, policy support, technical and industrial development trends, and the ways to accelerate the industrialization development, aiming to promote the development and improvement of IVD in China.

15.
Turk J Gastroenterol ; 32(2): 164-168, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33960940

RESUMEN

BACKGROUND: To investigate the predictive value of blood ammonia (BLA) quantification in the prognosis of acute liver failure (ALF). METHODS: Seventy-one patients with ALF were enrolled and BLA concentration was measured in all patients. After following up for 28 days, patients were divided into two groups: the surviving group (n = 21) and the deceased group (n = 50). An independent-samples t-test was used to compare BLA concentrations between the two groups, and receiver operating characteristic curves were used to ¬evaluate the predictive value of BLA in the prognosis of ALF. A fourfold table analysis was performed with the determined BLA cutoff value. RESULTS: The average concentration of BLA in the deceased group was significantly higher compared with the surviving group (144.50 µmol/L vs. 106 µmol/L, respectively; P = .035). The cutoff BLA concentration for a good ALF prognosis was 122.5 µmol/L. The area under the curve was 0.659. Both the sensitivity and specificity were >0.6. The 95% CIs for sensitivity and specificity were 0.452-0.733 and 0.477-0.878, respectively. The fourfold table analysis revealed a positive predictive value of 83.3%, a negative predictive value of 42.9%, a misdiagnosis rate of 28.6%, and an accuracy of 63.4%. CONCLUSION: With a cutoff BLA concentration of 122.5 µmol/L, the prognosis of ALF could be predicted with high sensitivity and specificity, a positive predictive value, a low misdiagnosis rate, and good accuracy.


Asunto(s)
Amoníaco , Fallo Hepático Agudo , Amoníaco/sangre , Humanos , Fallo Hepático Agudo/diagnóstico , Pronóstico , Curva ROC , Estudios Retrospectivos
16.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-888789

RESUMEN

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.


Asunto(s)
Animales , Humanos , Ratones , Apoptosis , Brucea/química , Glucógeno Sintasa Quinasa 3 , Células Jurkat , Fosfatidilinositol 3-Quinasas/genética , Aceites de Plantas/farmacología , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/genética , Semillas/química , Transducción de Señal
17.
Liver Int ; 41(5): 1033-1043, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33347692

RESUMEN

BACKGROUND: While CAR-T therapy has successfully treated haematological malignancies, it has proved sub-optimal for solid tumours. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumours. METHOD: We co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7 × 20). We test the anti-tumour ability in vitro and in vivo. Moreover the capacity of infiltration and proliferation of G3CAR-7 × 20 was measured. RESULT: We found (G3CAR-7 × 20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumour cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7 × 20 also increased the ability of CAR-T cells to infiltrate tumour tissue. CONCLUSION: co-expressed IL-7 and PH20 may significantly enhance the efficacy of targeted GPC3 CAR-T cells in solid tumours treatment.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Hialuronoglucosaminidasa/metabolismo , Inmunoterapia Adoptiva , Interleucina-7/metabolismo , Neoplasias/terapia , Receptores Quiméricos de Antígenos , Animales , Línea Celular Tumoral , Glipicanos , Humanos , Masculino , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto
18.
J Cell Mol Med ; 24(24): 14306-14315, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33135290

RESUMEN

Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up-regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up-regulate the expression of CDK16 by sponging miR-584-5p. The expression of miR-584-5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR-584-5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR-584-5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR-584-5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment.


Asunto(s)
Carcinoma Hepatocelular/genética , Quinasas Ciclina-Dependientes/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , ARN Circular/genética , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Interferencia de ARN , Activación Transcripcional , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-828630

RESUMEN

OBJECTIVE@#To study the clinical screening and genetic diagnosis of children suspected of Prader-Willi syndrome (PWS), as well as the differences in the scores of clinical diagnostic criteria among the children with a confirmed diagnosis of PWS.@*METHODS@#A total of 94 children suspected of PWS who were admitted from July 2016 to December 2018 were enrolled as subjects. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to confirm the diagnosis. For the children with a confirmed diagnosis of PWS, the scores of clinical diagnostic criteria were determined, and the perinatal characteristics were analyzed.@*RESULTS@#A total of 11 children with PWS were confirmed by MS-MLPA, with a detection rate of 12%, among whom there were 7 boys and 4 girls, with a median age of 3 years and 4 months (range 25 days to 6 years and 8 months) at the time of confirmed diagnosis. Among the 11 children with PWS, only 5 children (45%) met the criteria for clinical diagnosis. The main perinatal characteristics of the children with PWS were decreased fetal movement (9 cases, 82%), cesarean section birth (11 cases, 100%), hypotonia (11 cases, 100%), feeding difficulties (11 cases, 100%), and weak crying (11 cases, 100%).@*CONCLUSIONS@#Gene testing should be performed as early as possible for children suspected of PWS by clinical screening. PWS may be missed if only based on the scores of clinical diagnostic criteria.


Asunto(s)
Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Cesárea , Metilación , Hipotonía Muscular , Síndrome de Prader-Willi
20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-870654

RESUMEN

Four hundred and four male patients with primary gout were enrolled. According to the degree of nonalcoholic fatty liver diseases (NAFLD), the patients were divided into simple gout ( n=121), gout combined with mild NAFLD ( n=149) and gout combined with moderate-severe NAFLD ( n=134). The height, weight, waist, hip, blood pressure and blood biochemistry parameters of patients were measured. The degree of NAFLD was negatively correlated with the age of patients in three groups. The BMI, ratio of waist/hip, count of red cells, hemoglobin, hematocrit, red blood cell distribution width ( SD and CV), triglyceride, alanine aminotransferase and HOMA-IR were increased with the increasing of NAFLD severity (all P<0.05). Red blood cell count, hemoglobin, alanine aminotransferase, serum uric acid increased with the increasing of NAFLD severity (all P<0.05). Platelet, serum urea nitrogen and serum creatinine were decreased with the increase of NAFLD severity. Logistic regression showed that BMI, hemoglobin and HOMA-IR were independent risk factors for NAFLD. The prevalence and the severity of NAFLD was increased with increasing quadrates of hemoglobin. Taking group Q1 as a control, OR of NAFLD in group Q2 was 1.166(95 %CI:0.638-2.133), OR in group Q3 was 2.011(95 %CI:1.122-3.605)and OR in group Q4 was 3.120(95 %CI:1.613-6.034). The result indicates that hemoglobin levels are associated with the development and the severity of NAFLD in male patients with primary gout.

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