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1.
Analyst ; 146(9): 2807-2817, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949425

RESUMO

Self-assembled nanomaterials (SANs) exhibit designable biofunctions owing to their tunable nanostructures and modifiable surface. Various constituent units and multi-dimensional structures of SANs provide unlimited possibilities for numerous applications. This review emphasizes the recent development of SANs in the fields of biosensing, bioimaging, and nano-drug engineering. The unit type, design concepts, material advantages, assembly driving force, nanostructure effects, drug loading performance, etc. are discussed and summarized. Finally, we briefly summarize how to assemble unique nanomaterials and point out the key challenges in this field.

2.
Dis Colon Rectum ; 64(5): 555-562, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33939387

RESUMO

BACKGROUND: The advent of immune checkpoint inhibition therapy has dramatically improved survival in patients with skin melanoma. Survival outcomes after resection of anorectal melanoma treated with immune checkpoint inhibition have not been reported. OBJECTIVE: This study aimed to compare survival outcomes following surgical resection of anorectal melanoma between patients who received immune checkpoint inhibition and patients who did not. DESIGN: This study is a retrospective analysis of data from a prospectively maintained database. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Patients who underwent surgery for anorectal melanoma between 2006 and 2017 were included. They were stratified according to the use of immune checkpoint inhibition. MAIN OUTCOME MEASURES: The primary outcomes measured were overall and disease-specific survival. RESULTS: Of the 47 patients included in the analysis, 29 (62%) received immune checkpoint inhibition therapy. Twenty-two (76%) of the 29 patients received immune checkpoint inhibition after detection of metastasis or disease progression rather than in the neoadjuvant or adjuvant setting. Overall survival did not differ significantly between patients who received immune checkpoint inhibition therapy and patients who did not (median, 52 and 20 months; 5-year rate, 41% vs 35%; p = 0.25). Disease-specific survival also did not differ significantly. Our analysis did not identify any clinical or pathological features associated with response to immune checkpoint inhibition therapy or with survival. LIMITATIONS: This study was limited by its relatively small sample and retrospective design and by the heterogeneous treatment regimen in the immune checkpoint inhibition group. CONCLUSIONS: Immune checkpoint inhibition therapy by itself does not appear to improve survival in patients who undergo resection or excision of anorectal melanoma. Combinations of immune checkpoint inhibition with other therapeutic modalities warrant further investigation. See Video Abstract at http://links.lww.com/DCR/B499. MELANOMA DE LA MUCOSA ANORRECTAL EN LA ERA DE LOS INHIBIDORES DEL PUNTO DE CONTROL INMUNOLÓGICO: ¿DEBEMOS DE CAMBIAR NUESTRO PARADIGMA DEL MANEJO QUIRÚRGICO: El advenimiento de la terapia de los inhibidores del punto de control inmunológico, han mejorado dramáticamente la supervivencia en pacientes con melanoma de piel. No se han informado los resultados de supervivencia después de la resección del melanoma anorrectal, tratado con inhibidores del punto de control inmunológico.Comparar los resultados de supervivencia después de la resección quirúrgica de melanoma anorrectal entre pacientes que recibieron y no recibieron inhibidores del punto de control inmunológico.Análisis retrospectivo de una base de datos mantenida prospectivamente.Centro oncológico integral.Pacientes que se sometieron a cirugía por melanoma anorrectal entre 2006 y 2017. Los pacientes fueron estratificados según el uso de inhibidores del punto de control inmunológico.Supervivencia global y específica de la enfermedad.De los 47 pacientes incluidos en el análisis, 29 (62%) recibieron terapia de inhibidores del punto de control inmunológico. Veintidós (76%) de los 29 pacientes recibieron inhibidores del punto de control inmunológico después de la detección de metástasis o progresión de la enfermedad, en vez de administración adyuvante o neoadyuvante. La supervivencia global no varió significativamente entre los pacientes que recibieron o no recibieron terapia de inhibidores del punto de control inmunológico (mediana, 52 y 20 meses, respectivamente; tasa a 5 años, 41% frente a 35%, respectivamente; p = 0,25). La supervivencia específica de la enfermedad tampoco varió significativamente. Nuestro análisis no identificó ninguna característica clínica o patológica, asociada con la respuesta a la terapia de inhibidores del punto de control inmunológico o con la supervivencia.Muestra relativamente pequeña y diseño retrospectivo. Régimen de tratamiento heterogéneo en el grupo de inhibidores del punto de control inmunológico.La terapia por sí sola, de inhibidores del punto de control inmunológico, no parece mejorar la supervivencia en pacientes que se someten a resección o escisión de melanoma anorrectal. Las combinaciones de inhibidores del punto de control inmunológico con otras modalidades terapéuticas, merecen una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B499. (Traducción-Dr. Fidel Ruiz Healy).

3.
Dis Markers ; 2021: 6643586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791044

RESUMO

Purpose: To precisely quantify split glomerular filtration rate by Tc-99m-DTPA renal dynamic imaging and plasma clearance in order to increase its consistency among doctors. Methods: Tc-99m-DTPA renal dynamic imaging was performed according to the conventional radionuclide renal dynamic imaging by five double-blinded doctors independently and automatically calculated split GFR, namely, gGFR. Moreover, the conventional radionuclide renal dynamic imaging was assessed to only outline the kidney, blank background, and automatically calculated split GFR, gGFR'. The total GFR value of patients, tGFR, was obtained by the double-plasma method. According to the formula, Precise GFR (pGFR) = gGFR'/(gGFR' + gGFR') × tGFR. The precise GFR value of the divided kidney, pGFR, was calculated. The Kendall's W test was used to compare the consistency of gGFR and pGFR drawn by five physicians. Results: According to Kendall's W consistency test, Kendall's coefficient of concordance was 0.834, p = 0.0001 using conventional method. The same five doctors used blank background again and the same standard Gates method to draw the kidneys, which automatically calculated gGFR'. Using input formula, the pGFR was calculated and Kendall's W consistency test (Kendall's coefficient of concordance = 0.956, p = 0.0001). Conclusion: The combination of Tc-99m-DTPA renal dynamic imaging combined with the double-plasma method could achieve accurate split GFR, and because of the omission of influence factors, the consistency of pGFR obtained by different doctors using this method was significantly higher than that of conventional Tc-99m-DTPA renal dynamic imaging.

4.
Cancer Res ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853832

RESUMO

When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here we report that KMT2 mutations occur frequently in non-small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Furthermore, by disrupting homologous recombination (HR)-mediated DNA repair, KMT2C/D mutations sensitized NSCLC to Poly(ADP-Ribose) Polymerase inhibitors (PARPi), whose efficacy is unclear in NSCLC due to low BRCA1/2 mutation rates. These results demonstrate a novel, transcription-independent role of KMT2C in DDR and identify high-frequency KMT2C/D mutations as much-needed biomarkers for PARPi therapies in NSCLC and other cancers with infrequent BRCA1/2 mutations.

5.
Phys Rev E ; 103(3-1): 033305, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33862789

RESUMO

We use a convolutional neural network (CNN) and two logistic regression models to predict the probability of nucleation in the two-dimensional Ising model. The three methods successfully predict the probability for the nearest-neighbor Ising model for which classical nucleation is observed. The CNN outperforms the logistic regression models near the spinodal of the long-range Ising model, but the accuracy of its predictions decreases as the quenches approach the spinodal. An occlusion analysis suggests that this decrease is due to the vanishing difference between the density of the nucleating droplet and the background. Our results are consistent with the general conclusion that predictability decreases near a critical point.

6.
Spectrochim Acta A Mol Biomol Spectrosc ; 256: 119746, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33819763

RESUMO

Binding interaction between black phosphorus quantum dots (BPQDs) and trypsin was researched deeply to illustrate the variations on conformation and activity of trypsin affected by BPQDs via multi-spectroscopy and molecular modeling. Experimental results implied that inherent fluorescence of trypsin was quenched by BPQDs via static fluorescence quenching mode. BPQDs bound with trypsin to construct ground-state complex under the binding forces of van der Waal interaction and hydrophobic interaction, resulting in the conformational change of trypsin to be more hydrophilic and incompact. The result of molecular modeling indicated that BPQDs interacted with trypsin at its allosteric site and inhibited the activity of trypsin via non-competitive manner. Finally, BPQDs efficiently inhibited the digestion activity of trypsin on human serum albumin, human cervical carcinoma HeLa cells, and human lung adenocarcinoma A549 cells. This work not only explores the in-depth understanding on the influence of BPQDs on proteinases but also paves the way for further application of BPQDs on human beings for diseases treatments.

7.
J Pediatr Surg ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33840503

RESUMO

BACKGROUND: The medial segment as a mono-segmental graft was proposed to increase the donor pool for pediatric liver transplantation, but to date, there has been no published case. This study aims to revisit the feasibility of procuring the medial segment graft (MSG) by three-dimensional (3D) printing and ex vivo procedures performed on explanted diseased livers to overcome the gap between theory and clinical implementation. METHODS: From October 2004 to December 2016, we retrospectively analyzed preoperative computed tomography, magnetic resonance cholangiopancreatography, and intraoperative cholangiography images of our previous live liver donors and identified the indicated anatomy for the MSG, then materialized by 3D printing models to simulate the engraftment. Furthermore, we practiced the procurement procedures on selected explanted diseased livers. RESULTS: Among 291 analyzed livers, 96 livers (33%) met the arterial criteria for MSG, and two-thirds of them had ideal portal branches for reconstruction. The proposed right border of the MSG was the Cantlie's line, and the left edge was the right side of the umbilical fissure. The mean estimated volume of the MSG was 234 ± 54 ml. Besides, we suggest implanting the MSG as an auxiliary partial graft in an inverted vertical position or a standalone graft with right-side rotation in the right subphrenic space. CONCLUSION: The procurement of the MSG is feasible based on our results. However, due to the novelty of the procedure, we suggest that the first attempted case of MSG should be implanted as an auxiliary partial graft to maximize patient safety. LEVEL OF EVIDENCE: Type of study: Case series with no comparison groups EVIDENCE LEVEL: Level IV.

8.
J Biomater Sci Polym Ed ; : 1-13, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830881

RESUMO

The application of 3D printing technology in tissue engineering has become increasingly important. However, due to the limitations of bio-ink, there are still some remaining problems. For example, the major challenge for ideal bio-ink is to maintain stable 3D structure and good biocompatibility in the meantime while conventional gels are week and nearly unprintable. So, the development of new bio-ink material with improved rheological and mechanical properties is highly demanded to avoid compromising biocompatibility for tissue engineering. Silk fibroin (SF), a natural degradable polymer, is considered to be a proper material for the preparation of bio-inks. We used SF, gelatin, and polyols as raw materials to fabricate bio-inks and scaffolds. We evaluated the rheological properties and printability of bio-inks with a rotational rheometer and a 3D printer. The scaffolds were prepared by crosslinking and freeze-drying technologies. The biocompatibility and osteoinductive functions of scaffolds were investigated by evaluating proliferation, osteogenic differentiation and related cell signaling of cultured MC3T3-E1 cells. The results showed that the scaffolds using SF, Gel and propanediol (PG) not only had good rheological properties and storage modulus, but also could better enhance osteogenic specific genes expression mediated by Smad1/5/8 and Runx2 pathways. What is more, morphological characterization showed that α-mem incubation could help scaffold form porous structure on its surface, which could shed a light on a new 3D bio-printed bone repair scaffold with both naturally emerged and CAD-designed porous structure. Our findings provide a potential biomaterial for the treatment of bone tissue regeneration.

9.
Anal Chim Acta ; 1157: 338377, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33832590

RESUMO

In this fundamental research, we found that homo-oligo based dsDNA holds potential electrochemical characteristics in comparison to hetero-oligo based dsDNA which can be exploited in voltammetric and impedimetric biosensors. We prepared a homo-oligo based dsDNA from 20 deoxyribonucleotides of adenine, guanine, cytosine, and thymine (A20, G20, C20, and T20 respectively) and a hetero-oligo based dsDNA from two partially complementary oligos (5'-TTT TTT CAT CTA TCA ACA TCA GTC TGA TAA GCT ATA GAA GC-3' and 5'-TTT TTT ATA GCT TTG ATA GA-3'. Electrochemical impedance spectroscopy in 1 mM 0.1 M K3[Fe(CN)6]/KCl showed that Au working electrode modified with hetero-oligo based dsDNA (Au/hetero-oligo-dsDNA) was more resistive toward charge transfer of Fe(CN)63-/4- compared to Au working electrode modified with homo-oligo based dsDNA (Au/homo-oligo-dsDNA). Additionally, cyclic voltammetry and linear sweep voltammetry showed that Au/homo-oligo-dsDNA produced quantifiable anodic and cathodic peak currents which were not observed for Au/hetero-oligo-dsDNA. Nyquist and Bode plots derived from electrochemical impedance spectroscopy on three different electroactive areas (0.0705, 0.0747 and 0.0837 cm2) of Au working electrode showed no significant change in the capacitive behavior of Au/homo-oligo-dsDNA and Au/hetero-oligo-dsDNA in a linear range of frequency (10-100 Hz).

10.
Sci Signal ; 14(678)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850055

RESUMO

The RIG-I-like receptor (RLR) signaling pathway is pivotal for innate immunity against invading viruses, and dysregulation of this molecular cascade has been linked to various diseases. Here, we identified dimethylarginine dimethylaminohydrolase 2 (DDAH2) as a potent regulator of the RLR-mediated antiviral response in human and mouse. Overexpression of DDAH2 attenuated RLR signaling, whereas loss of DDAH2 function enhanced RLR signaling and suppressed viral replication ex vivo and in mice. Upon viral infection, DDAH2 relocated to mitochondria, where it induced the production of nitric oxide (NO) and the activation of dynamin-related protein 1 (Drp1), which promoted mitochondrial fission and blocked the activation of innate immune responses mediated by mitochondrial antiviral signaling (MAVS). TANK-binding kinase 1 (TBK1), a kinase downstream of MAVS, inhibited DDAH2 by phosphorylating DDAH2 at multiple sites. Our study thus identifies a reciprocal inhibitory loop between the DDAH2-NO cascade and the RLR signaling pathway that fine-tunes the antiviral immune response.

11.
Gynecol Endocrinol ; : 1-6, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33904356

RESUMO

OBJECTIVE: The genetic basis of fertilization failure after intracytoplasmic sperm injection (ICSI) is largely unknown and the aim of this study is to investigate the genetic causes of fertilization failure in primary infertile women. METHODS: Six affected women diagnosed with infertility and fertilization failure were recruited. The genetically pathogenic factor of their fertilization failures were investigated by clinical exome sequencing. One hundred healthy controls were verified by Sanger sequencing. RESULTS: Novel compound heterozygous mutations c.625G > T and c.759-2A > G of WEE2 in one affected individual were revealed by clinical exome sequencing. Trios analysis of the mutations represented an autosomal recessive pattern. The nonsense mutation c.625G > T (p.Glu209*) indicated the truncation of the WEE2 protein and c.759-2A > G was predicted to affect the splicing. CONCLUSIONS: The novel variants extend the spectrum of WEE2 mutations, which promotes the prognostic value of testing for WEE2 mutations in infertile women with fertilization failure.

12.
Cardiovasc Toxicol ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929718

RESUMO

Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family and plays a vital role in the metabolism of fatty acids. However, few studies have examined the role of FABP5 in pathological cardiac remodeling and heart failure. The aim of this study was to explore the role of FABP5 in transverse aortic constriction (TAC)-induced pathological cardiac remodeling and dysfunction in mice. Quantitative RT-PCR (qRT-PCR) and western blotting (WB) analysis showed that the levels of FABP5 mRNA and protein, respectively, were upregulated in hearts of the TAC model. Ten weeks after TAC in FABP5 knockout and wild type control mice, echocardiography, histopathology, qRT-PCR, and WB demonstrated that FABP5 deficiency aggravated cardiac injury (both cardiac hypertrophy and fibrosis) and dysfunction. In addition, transmission electron microscopy, ATP detection, and WB revealed that TAC caused severe impairment to mitochondria in the hearts of FABP5-deficient mice compared with that in control mice. When FABP5 was downregulated by siRNA in primary mouse cardiac fibroblasts, FABP5 silencing increased oxidative stress, reduced mitochondrial respiration, and increased the expression of myofibroblast activation marker genes in response to treatment with transforming growth factor-ß. Our findings demonstrate that FABP5 deficiency aggravates cardiac pathological remodeling and dysfunction by damaging cardiac mitochondrial function.

13.
Pediatrics ; 147(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33888566

RESUMO

CONTEXT: In several studies, authors have reported on cognitive behavioral therapy (CBT) for children and adolescents with autism spectrum disorders (ASDs), but inconsistent treatment effectiveness was revealed from these studies. OBJECTIVE: To evaluate the effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD by using a meta-analytic approach. DATA SOURCES: Data sources included PubMed, Embase, and the Cochrane Library. STUDY SELECTION: We selected randomized controlled trials (RCTs) in which authors reported effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD from database inception to May 2019. DATA EXTRACTION: For each study, 2 authors extracted data on the first author's surname, publication year, country, sample size, mean age, CBT target, intervention, outcome measurement, follow-up duration, and investigated outcomes. RESULTS: Forty-five RCTs and 6 quasi RCTs of 2485 children and adolescents with ASDs were selected for the final meta-analysis. There was no significant difference between CBT and control for symptoms related to ASD based on self-reported outcomes (standard mean difference: -0.09; 95% confidence interval: -0.42 to 0.24; P = .593), whereas CBT significantly improved the symptoms related to ASD based on informant-reported outcomes, clinician-rated outcomes, and task-based outcomes. Moreover, the pooled standard mean differences indicated that CBT has no significant effect on symptoms of social-emotional problems based on self-reported outcomes. LIMITATIONS: The quality of included studies was low to modest, significant heterogeneity among the included studies for all investigated outcomes was detected, and publication bias was inevitable. CONCLUSIONS: These findings indicate that CBT may significantly improve the symptoms of ASD and social-emotional problems in children or adolescents with ASD.

14.
J Healthc Eng ; 2021: 5553029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868620

RESUMO

Postoperative cognitive dysfunction (POCD) refers to the complications of the central nervous system before and after surgery in patients without mental disorders. Many studies have shown that surgical anesthesia may cause POCD, especially in elderly patients. This article aims to study the relationship between artificial intelligence-based general anesthetics and postoperative cognitive dysfunction. This article first describes and classifies artificial intelligence, introduces its realization method, machine learning algorithms, and briefly introduces the basic principles of regression and classification methods in machine learning; then, the principles and techniques of general anesthetics are proposed. The pathogenesis of postoperative cognitive dysfunction (POCD) is explained in detail. Finally, the effect of anesthetics on postoperative cognitive dysfunction is obtained from both inhaled anesthetics and intravenous anesthetics. The impact on postoperative cognitive function is explained. The experimental results in this article show that there is no statistically significant difference in the two groups of patients' age, gender ratio, body mass index, education level, preoperative comorbidities, and other general indicators. Through the use of EEG bispectral index monitors to monitor the depth of anesthesia and postoperative cognitive dysfunction, first, there was no obvious relationship between the occurrence of postoperative cognitive dysfunction at 1, 5, 10, and 50 days and discharge time. The comprehensive monitoring group can reduce the clinical dose of preventive medication and cis-atracurium and shorten the patient's recovery time, extubation time, and recovery time. In addition, it can also reduce the increase of serum protein S100ß in elderly patients and reduce the incidence of early postoperative cognitive dysfunction.

15.
Medicine (Baltimore) ; 100(16): e25593, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879721

RESUMO

BACKGROUND: To systematically evaluate the effectiveness and safety of traditional Chinese medicine preparation XPYEG combined with SBI and SBI alone in the treatment of REC, and to provide the reference in drugs for the clinical treatment of children with rotavirus enteritis. METHODS: Retrieving the English databases: PubMed, Cochrane Library and Embase; Chinese databases: CNKI, CBM and WANFANG Data. Retrieving a randomized controlled trial of XPYEG and SBI in the treatment of REC. The retrieval time is from the above database until September 2020. The retrieval strategy of combining free words and subject words is adopted, and the references included in the literature are searched manually in accordance with the literature studied in this paper and not included in the above database. Two researchers screen the literature according to the literature inclusion and exclusion criteria, extract valid data and evaluate the quality of the literature, and cross-check it. Using the RevMan 5.3 software to conduct the meta-analysis on the main outcome and secondary outcome indicators of the included literature, while assessing the evidence quality of included study. RESULTS: The effectiveness and safety of XPYEG and SBI in the treatment of REC are presented through the main and secondary outcome indicators. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/3QSZG. CONCLUSION: This study will conclude whether the combination of XPYEG and SBI is more effective than SBI alone in the treatment of REC, and whether the medication increases the risk of adverse reactions compared with single medication. ETHICS AND DISSEMINATION: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Enterite/terapia , Probióticos/administração & dosagem , Infecções por Rotavirus/terapia , Saccharomyces boulardii , Pré-Escolar , Enterite/virologia , Feminino , Humanos , Lactente , Masculino , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Infecções por Rotavirus/virologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
16.
Cancer Biother Radiopharm ; 36(2): 133-142, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33646017

RESUMO

Background: Patients with osteoblastic bone metastases are candidates for radium-223 (223RaCl2) therapy and may undergo sodium fluoride-18 (18F-NaF) positron emission tomography-computed tomography imaging to identify bone lesions. 18F-NaF has been shown to predict 223RaCl2 uptake, but intratumor distributions of these two agents remain unclear. In this study, the authors evaluate the spatial distribution and relative uptakes of 18F-NaF and 223RaCl2 in Hu09-H3 human osteosarcoma mouse xenograft tumors at macroscopic and microscopic levels to better quantify their correlation. Materials and Methods: 18F-NaF and 223RaCl2 were co-injected into Hu09-H3 xenograft tumor severe combined immunodeficient mice. Tumor content was determined from in vivo biodistributions and visualized by PET, single photon emission computed tomography, and CT imaging. Intratumor distributions were visualized by quantitative autoradiography of tumor tissue sections and compared to histology of the same or adjacent sections. Results: 18F and 223Ra accumulated in proportional amounts in whole Hu09-H3 tumors (r2 = 0.82) and in microcalcified regions within these tumors (r2 = 0.87). Intratumor distributions of 18F and 223Ra were spatially congruent in these microcalcified regions. Conclusions: 18F-NaF and 223RaCl2 uptake are strongly correlated in heterogeneously distributed microcalcified regions of Hu09-H3 xenograft tumors, and thus, tumor accumulation of 18F is predictive of 223Ra accumulation. Hu09-H3 xenograft tumors appear to possess certain histopathological features found in patients with metastatic bone disease and may be useful in clarifying the relationship between administered 223Ra dose and therapeutic effect.

17.
Zhongguo Zhen Jiu ; 41(2): 155-60, 2021 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-33788462

RESUMO

OBJECTIVE: To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared. RESULTS: Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (P<0.05), and NO was increased (P<0.05) in the two groups; FPG, 2hPG, FINS and HOMA-IR after treatment were decreased in the IGT group (P<0.05), the improvement of the above indexes in the IGT group was more significant than that in the NGT group (P<0.05). After treatment, the serum levels of ADMD, ET-1 and MDA were decreased (P<0.05), and NO was increased (P<0.05) in the obese subgroup. In the IGT group, the improvement of serum ADMD, ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). In the NGT group, the improvement of ET-1, MDA and NO in the obese subgroup was more significant than that in the non-obese subgroup (P<0.05). CONCLUSION: Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.


Assuntos
Terapia por Acupuntura , Intolerância à Glucose , Resistência à Insulina , Síndrome do Ovário Policístico , Glicemia , Feminino , Glucose , Intolerância à Glucose/terapia , Humanos , Insulina , Síndrome do Ovário Policístico/terapia
18.
J Immunol Res ; 2021: 6694392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728352

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies and is known for its high resistance and low response to treatment. Tumor immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Karyopherin alpha 2 (KPNA2), a member of the nuclear transporter family, is elevated in multiple human cancers and accelerates carcinogenesis. However, the specific role of KPNA2 in PDAC remains unclear. In this study, we found that expression of KPNA2 was significantly upregulated in PDAC compared to adjacent nontumor tissue and its high expression was correlated with poor survival outcome by analyzing the GEO datasets. Similar KPNA2 expression pattern was also found in both human patient samples and KPC mouse models through IHC staining. Although KPNA2 knockdown failed to impair the vitality and migration ability of PDAC cells in vitro, the in vivo tumor growth was significantly impeded and the expression of immune checkpoint ligand PD-L1 was reduced by silencing KPNA2. Furthermore, we uncovered that KPNA2 modulated the expression of PD-L1 by mediating nuclear translocation of STAT3. Collectively, our data suggested that KPNA2 has the potential to serve as a promising biomarker for diagnosis in PDAC.

19.
Chin J Nat Med ; 19(3): 188-194, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781452

RESUMO

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 µg·kg-1·d-1) induced the occurrence of cholestasis in female Wistar rats, as evidenced by increased serum levels of γ-glutamyl transpeptidase (γ-GGT), alkaline phosphatase (ALP) and hepatic total bile acids (TBAs). In addition, the heptocyte polarity associated with the strcture of tight junctions (TJs) was disrupted in both rats and sandwich-cultured primary hepatocytes. Immunoblotting revealed decreased expression of the TJ-associated proteins occludin, claudin-1, and zonula occludens protein (ZO-1), and downregulated mRNA levels of these TJs was also detected by real-time PCR. An immunofluorescence analysis showed abnormal subcellular localization of occludin, claudin-1 and ZO-1, which was also confirmed by transmission electron microscopy. Moreover, the concentration of FITC-dextran, a marker of paracellular penetration, was found to increase rapidly in bile increased rapidly (within 6 minutes) after treatment with TP, which indicated the functional impairment of TJs. Taken together, these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver, and the increased paracellular permeability might play an important role in these pathological changes.

20.
Sci Rep ; 11(1): 6540, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753862

RESUMO

We aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan-Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098-1.752; p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047-1.320; p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.

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