[Retracted] MicroRNA­106a­5p promotes the proliferation, autophagy and migration of lung adenocarcinoma cells by targeting LKB1/AMPK.

[This retracts the article DOI: 10.3892/etm.2021.10857.].

Comparison of Lugano Criteria Versus RECIL and PERCIST as Prognostic Factors in Diffuse Large B-Cell Lymphoma.

OBJECTIVE: This study aimed to compare the criteria of the Lugano, RECIL, and PERCIST for prognosis in patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: We retrospectively evaluated 335 patients with diffuse large B-cell lymphoma. All patients underwent baseline 18 F-FDG PET/CT. Among them, 252 and 213 patients underwent interim PET/CT (I-PET/CT) and end-of-treatment PET/CT (EoT-PET/CT), respectively. Scans were interpreted by 2 nuclear medicine physicians using Lugano, RECIL, and PERCIST. RECIL and PERCIST were compared with Lugano for predicting progression-free survival (PFS) and overall survival (OS). RESULTS: All 3 response criteria could be used to predict PFS and OS. In I-PET/CT, the concordance index of Lugano in predicting PFS and OS was higher than that of RECIL (both P = 0.043) or PERCIST ( P = 0.008 and P = 0.034, respectively). In EoT-PET/CT, the concordance index of Lugano for predicting PFS and OS was similar to RECIL and not significantly different from PERCIST ( P = 0.597 and P = 0.231, respectively). CONCLUSIONS: For I-PET/CT, using the Lugano criteria is more accurate than RECIL or PERCIST in predicting PFS and OS. However, for EoT-PET/CT, the PERCIST criteria are minimally better.

Physiological Uptake Characteristics of Breast on 68Ga-FAPI-04 PET/CT.

PURPOSE: Gallium 68 (68Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological 68Ga-FAPI-04 uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological 68Ga-FAPI-04 uptake in normal breast. PROCEDURES: A total of 143 consecutive women with 68Ga-FAPI-04 PET/CT data were reviewed retrospectively. SUVmax, density and thickness of breast, as well as SUVmax of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs. RESULTS: Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast. There was no difference in 68Ga-FAPI-04 uptake between bilateral breasts (right: median, 1.14[IQR, 0.85-1.54] vs. left: median, 1.09[IQR, 0.86-1.54]; P = 0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median SUV, 3.91 [IQR, 2.85-4.35]) than those with expected moderate (early follicular, early luteal and late luteal phases; median SUV, 1.57 [IQR, 1.39-2.08]; P < 0.001) or low level (menopause and post-operation; median SUV, 0.98 [IQR, 0.83-1.21]; P < 0.001). Menstrual status was an independent predictors of breast SUV (r2 = 0.689, P < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status (P = 0.913).

PET/CT Showing a Case of Langerhans Cell Histiocytosis Involving the Pleura.

ABSTRACT: We describe a case of Langerhans cell histiocytosis involving the bilateral pleura on FDG PET/CT. Multiple pleural nodules were detected by CT in a 38-year-old woman with chest pain and night sweats. Malignant tumors were suspected. PET/CT showed abnormal FDG uptake in those pleural lesions. No other abnormal foci were seen in the rest of the whole body. A primary pleural disease was considered. Then the histopathologic findings after biopsy confirmed the diagnosis of Langerhans cell histiocytosis.

Ultrasonographic measurement of the effect of physical training on ligament injuries / Medição ultrassonográfica do efeito do treinamento físico nas lesões ligamentares / Medición ecográfica del efecto del entrenamiento físico en las lesiones de ligamentos

ABSTRACT Introduction: The ankle joint is the most load-bearing joint of the human body. The health consciousness of people is increasing day by day, the probability of ankle sports injuries is also increasing. Objective: Analyze the applying sports medicine ultrasound value to rehabilitate anterior talofibular tendon injury. Methods: Seventy- two patients with anterior talofibular injury in a particular hospital were divided into control and observation groups to observe the effect of recovery, recovery time, and degree of ligament injury during rehabilitation treatment. Results: In the observation group, the complete recovery rate was 91.67%, incomplete recovery (8.33%), recovery time was (2.36±0.9) months. The complete recovery rate of the control group is (77.78%), the incomplete recovery (22.2%), the recovery time (3.58±0.42) months. Patients in the experimental group had a higher grade of ligament injury III than those in the control group during each rehabilitation period; the difference was statistically significant (P<0.05). Conclusions: Sports medical ultrasound can determine the degree of anterior talofibular ligament rupture after injury, providing a basis for the clinical formulation of the treatment plan. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução: A articulação do tornozelo é a articulação do corpo humano que mais suporta carga. A consciência da saúde das pessoas está aumentando de dia para dia, a probabilidade de lesões esportivas no tornozelo também está aumentando. Objetivo: Analisar o valor de aplicação do ultra-som de medicina esportiva para a reabilitação de lesão no tendão talofibular anterior. Métodos: Setenta e dois pacientes com lesão talofibular anterior em um determinado hospital foram divididos em grupos de controle e observação para observar o efeito da recuperação, o tempo de recuperação e o grau de lesão ligamentar durante o tratamento da reabilitação. Resultados: No grupo de observação, a taxa de recuperação completa foi de 91,67%, a recuperação incompleta (8,33%), o tempo de recuperação foi de (2,36±0,9) meses. A taxa de recuperação completa do grupo de controle é de (77,78%), a recuperação incompleta (22,2%), o tempo de recuperação (3,58±0,42) meses. Os pacientes do grupo experimental tiveram maior grau de lesão ligamentar III do que os do grupo controle durante cada período de reabilitação, a diferença foi estatisticamente significativa (P<0,05). Conclusões: A ultra-sonografia médica esportiva pode determinar o grau de ruptura do ligamento talofibular anterior após a lesão, fornecendo uma base para a formulação clínica do plano de tratamento. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción: La articulación del tobillo es la que más carga soporta del cuerpo humano. La conciencia de la salud de las personas aumenta día a día, la probabilidad de lesiones deportivas en el tobillo también aumenta. Objetivo: Analizar el valor de la aplicación de ultrasonidos en medicina deportiva para la rehabilitación de la lesión del tendón talofibular anterior. Métodos: Setenta y dos pacientes con lesión talofibular anterior en un hospital particular fueron divididos en grupos de control y de observación para observar el efecto de la recuperación, el tiempo de recuperación y el grado de lesión del ligamento durante el tratamiento de rehabilitación. Resultados: En el grupo de observación, la tasa de recuperación completa fue del 91,67%, la recuperación incompleta (8,33%), el tiempo de recuperación fue de (2,36±0,9) meses. La tasa de recuperación completa del grupo de control fue (77,78%), la recuperación incompleta (22,2%), el tiempo de recuperación (3,58±0,42) meses. Los pacientes del grupo experimental tuvieron un mayor grado de lesión del ligamento III que el grupo de control durante cada periodo de rehabilitación, la diferencia fue estadísticamente significativa (P<0,05). Conclusiones: La ecografía médico-deportiva puede determinar el grado de rotura del ligamento talofibular anterior tras la lesión, proporcionando una base para la formulación clínica del plan de tratamiento. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

MicroRNA-106a-5p promotes the proliferation, autophagy and migration of lung adenocarcinoma cells by targeting LKB1/AMPK.

It has previously been reported that lung cancer has the highest morbidity and mortality rate worldwide; however, the pathogenesis underlying lung cancer has not been fully elucidated. The aim of the present was primarily to assess the influence of microRNA (miR)-106a-5p on the biological behaviors of lung cancer cells. In the present study, bioinformatics analysis was used to analyze the expression characteristics of miR-106a-5p and its relationship with the prognosis of patients with lung adenocarcinoma (LUAD) in The Cancer Genome Atlas. A dual luciferase reporter assay was performed to verify the binding of miR-106a-5p and liver kinase B1 (LKB1). The Cell Counting Kit-8, colony formation and Transwell assays were utilized to detect cell viability, proliferation and migration, respectively. Protein and RNA expression levels were examined by western blotting and reverse transcription-quantitative PCR analysis, respectively. It was observed that miR-106a-5p was highly expressed in LUAD and associated with poor prognosis. miR-106a-5p promoted the proliferation and migration of LUAD cells, and inhibited autophagy. By contrast, LKB1 inhibited cell proliferation and migration, promoted autophagy and blocked the cancer-promoting effects of miR-106a-5p. Overexpression of miR-106a-5p inhibited the phosphorylation of AMP-activated protein kinase (AMPK) and tuberin (TSC2), and promoted the phosphorylation of mTOR. By contrast, overexpression of LKB1 blocked the promotion of mTOR phosphorylation, and the inhibition of AMPK and TSC2 phosphorylation caused by miR-106a-5p. In summary, the results of the present study indicated that miR-106a-5p regulated the phosphorylation of the AMPK pathway by targeting LKB1, and was involved in the proliferation, migration and autophagy of LUAD cells.

Intrasellar Cephalocele.

Intrasellar cephalocele is very rare and is often overlooked because of its atypical clinical demonstration. A 2-year, 10-month-old girl was referred to our hospital with short stature. Magnetic resonance imaging revealed an extension of the anterior third ventricle, which protruded into the pituitary fossa, but not into the craniopharyngeal canal, sphenoid bone, or sphenoid sinus. In addition, there was no bony defect of the floor of the sellar turcica or the sphenoid sinus, and the mass was not protruding into the nasal cavity or nasopharynx. Thus the patient was clinically diagnosed with intrasellar cephalocele, which is considered as a rare subtype of transsphenoidal cephalocele. Instead of surgical intervention, the patient was given growth hormone replacement therapy. After 1-year follow-up, the patient had significant increase in height.

Correlation between DNA methylation and Thymic Stromal Lymphopoietin expression in asthmatic airway epithelial cells.

BACKGROUND: The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear. OBJECTIVE: This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells. METHODS: Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 µg/mL) for 12 h (37 °C, 5% CO2). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting. RESULTS: Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH. CONCLUSIONS: Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.

Control of Treg cell homeostasis and immune equilibrium by Lkb1 in dendritic cells.

To balance immunity and tolerance, the endogenous pool of Foxp3+ regulatory T (Treg) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of Treg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive Treg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, Treg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in Treg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling Treg cell homeostasis, immune response and tolerance.

Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer.

AIM: IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects. METHODS: IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected. RESULTS: IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02 ± 0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4(+) T cell proliferation without affecting CD8(+) T cell proliferation. CONCLUSION: IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.

[Mesenchymal stem cells promote mouse breast tumor progression by inducing the suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells].

OBJECTIVE: To investigate the role of mesenchymal stem cells (MSCs) in tumor progression by inducing immuno-suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells (BM-CD11b⁺ Gr1⁺ cells). METHODS: After co-cultured with MSCs, the immunophenotypes of BM-CD11b⁺ Gr1⁺ cells were tested by flow cytometry. The influence of MSCs on CD11b⁺ Gr1⁺ cells was evaluated by T cell proliferation assay after cultured with or without MSCs. The mouse 4T1 breast tumor model was established to explore the effect on tumor growth. RESULTS: MSCs promoted the survival of CD11b⁺ Gr1⁺ cells and induced the generation of CD11b⁺ Gr1⁺ cells from CD11b⁻ Gr1⁻ cells sorted from bone marrow. MSCs also enhanced the ability of BM-CD11b⁺ Gr1⁺ cells to suppress T cell proliferation and activation. CD11b⁺ Gr1⁺ cells after co-cultured with MSCs promoted 4T1 tumor growth and accelerated death of tumor-bearing mice. CONCLUSION: MSCs can promote tumor progression by inducing suppressive function of myeloid-derived CD11b⁺ Gr1⁺ cells from bone marrow.

Programming of the development of tumor-promoting neutrophils by mesenchymal stromal cells.

BACKGROUND/AIMS: Neutrophils obtain immunosuppressive function during tumor development, yet the mechanisms are largely unknown. This study explored whether and how mesenchymal stromal cells (MSCs), the key component of tumor microenvironment, regulate the suppressive function of neutrophils. METHODS: Immunosuppressive function of neutrophils was evaluated by T cell proliferation assay and 4T1 breast tumor model; molecular mechanisms were explored by transcriptional profiling, Real-time RT-PCR, arginase activity assay, and iNOS inhibition experiments. RESULTS: After being cocultured with MSCs primed by TNF-α (TNF-MSCs), CD11b(+)Ly6G(+) neutrophils isolated from bone marrow of normal mice or spleen of tumor-bearing mice obtained immunosuppressive function to inhibit T cell proliferation in vitro, and to enhance 4T1 tumor progression in vivo. Moreover, arginase activity and expression of iNOS, saa3, some cytokines and chemokines and their receptors, were upregulated in neutrophils after co-culture with TNF-MSCs. Inhibition of iNOS activity attenuated the suppressive effect of TNF-MSC pre-cocultured neutrophils on T cell proliferation. CONCLUSION: MSCs program neutrophils into an immunosuppressive and tumor-promoting phenotype.

Simultaneous removal of coexistent heavy metals from simulated urban stormwater using four sorbents: a porous iron sorbent and its mixtures with zeolite and crystal gravel.

The selectivity sequence and removal of coexistent heavy metals (namely As, Cd, Cr, Cu, Ni and Zn) in synthetic urban stormwater runoff were investigated by adsorption onto a porous iron sorbent (namely P1) and its mixtures with zeolite and crystal gravel, respectively (namely P2, P3, and P4). A batch method was employed to simulate the sorption processes. The geochemical model PHREEQC was used to calculate the metals' species and saturation data for elucidating the sorption data. The equilibrium data demonstrated a good fit with the Freundlich model and showed affinity in the orders: Cd>Zn>Ni>Cu>As>Cr (sorbents P1, P3 and P4) and Cd>Zn>Ni>As>Cu>Cr (sorbent P2). In addition to this, Calculated Distribution Coefficient (K(d)) values were used to compare the overall heavy metal removal efficiencies of the sorbents, which, in decreasing order, was found to be P4>P1>P2>P3. In comparing these four commercial sorbents, sorbent P4 represents a promising material for treatment of urban stormwater runoff containing mixed heavy metals.