MRI radiomics predicts the efficacy of EGFR-TKI in EGFR-mutant non-small-cell lung cancer with brain metastasis.

AIM: To develop and validate models based on magnetic resonance imaging (MRI) radiomics for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases. MATERIALS AND METHODS: 117 EGFR-mutant NSCLC patients with brain metastases who received EGFR-TKI treatment were included in this study from January 1, 2014 to December 31, 2021. Patients were randomly divided into training and validation cohorts in a ratio of 2:1. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) algorithm. Logistic regression analysis and Cox proportional hazard regression analysis were used to screen clinical risk factors. Clinical (C), radiomics (R), and combined (C + R) nomograms were constructed in models predicting short-term efficacy and intracranial progression-free survival (iPFS), respectively. Calibration curves, Harrell's concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of models. RESULTS: Overall response rate (ORR) was 57.3% and median iPFS was 12.67 months. The C + R nomograms were more effective. In the short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.860 (0.820-0.901, 95%CI) and 0.843 (0.783-0.904, 95%CI). In iPFS model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.837 (0.751-0.923, 95%CI) and 0.850 (0.763-0.937, 95%CI). CONCLUSION: The C + R nomograms were more effective in predicting EGFR-TKI efficacy of EGFR-mutant NSCLC patients with brain metastases than single clinical or radiomics nomograms.

[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Remnant cholesterol is associated with hip BMD and low bone mass in young and middle-aged men: a cross-sectional study.

PURPOSE: Remnant cholesterol (RC) is a contributor to cardiovascular diseases, obesity, diabetes, and metabolic syndrome. However, the specific relationship between RC and bone metabolism remains unexplored. Therefore, we aimed to investigate the relationships of RC with hip bone mineral density (BMD) and the risk of low bone mass. METHODS: Physical examination data was collected from men aged < 60 years as part of the Kailuan Study between 2014 and 2018. The characteristics of the participants were compared between RC quartile groups. A generalized linear regression model was used to evaluate the relationship between RC and hip BMD and a logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for low bone mass. Additional analyses were performed after stratification by body mass index (BMI) (≥ or < 24 kg/m2). Sensitivity analyses were performed by excluding individuals who were taking lipid-lowering therapy or had cancer, cardiovascular diseases, or diabetes. RESULTS: Data from a total of 7,053 participants were included in the analysis. After adjustment for confounding factors, RC negatively correlated with hip BMD (ß = - 0.0079, 95% CI: - 0.0133, - 0.0025). The risk of low bone mass increased from the lowest to the highest RC quartile, with ORs of 1 (reference), 1.09 (95% CI: (0.82, 1.44), 1.35 (95%CI: 1.02, 1.77), and 1.43 (95% CI: 1.09, 1.89) for Q1, Q2, Q3, and Q4, respectively (P for trend = 0.004) in the fully adjusted model. Compared to RC < 0.80 mmol/l group, the risk of low bone mass increased 39% in RC ≥ 0.80 mmol/l group (P < 0.001). The correlation between RC and hip BMD was stronger in participants with BMI ≥ 24 kg/m2 group (ß = - 0.0159, 95% CI: - 0.0289, - 0.0029). The results of sensitivity analyses were consistent with the main results. CONCLUSION: We have identified a negative correlation between serum RC and hip BMD, and a higher RC concentration was found to be associated with a greater risk of low bone mass in young and middle-aged men.

Comparison of different dosages of propofol combined with its equivalent alfentanil in outpatient abortion: a prospective, double-blinded, randomized trial.

OBJECTIVE: This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. PATIENTS AND METHODS: The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 µg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality. RESULTS: The ED50 and the ED95 values of alfentanil were 3.37 µg·kg-1 (95% CI: 2.58-3.97 µg·kg-1) and 4.68 µg·kg-1 (95% CI: 4.04-9.32 µg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes. CONCLUSIONS: The combination of 2.5 mg·kg-1 propofol and 4.68 µg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 µg·kg-1 alfentanil without increasing additional risks associated with anesthesia.

Gold(I) ion and the phosphine ligand are necessary for the anti-Toxoplasma gondii activity of auranofin.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

Incidence, factors, and prognostic analyses of challenging cardiopulmonary bypass separation in Chinese cardiac surgical populations.

BACKGROUND: Challenging separation from cardiopulmonary bypass (CPB) has been associated with multiple medical adversities, while its incidence, associated factors, and prognosis among cardiac surgery populations are substantially understudied. METHODS: Adult cardiac surgical patients in two medical centers were retrospectively analyzed. Separation from CPB was stratified as easy, difficult, or complex, based on the use of pharmacologic assistance agents and mechanical supports. The various in-hospital adverse outcomes (e.g., mortality, common complications) were assessed. RESULTS: The incidence of difficult and complex separation from CPB was 21.9% (1159 cases, 95% CI 20.8% to 23.1%), and 6.1% (320 cases, 95% CI 5.4% to 6.7%), respectively. High age, the presence of pulmonary hypertension or unstable angina, decreased ejection fraction, and emergency surgery were more frequently associated with challenging separation from CPB. Patients who experienced challenging separation from CPB had an elevated risk of adverse outcomes, including in-hospital mortality (complex: odds ratio [OR] 2.85), composite infection events (difficult: OR=1.82; complex: OR=1.88), major adverse cardiac events (difficult: OR=1.40; complex: OR=1.57), pulmonary complications (difficult: OR=1.31; complex: OR=1.20), acute kidney injury (difficult: OR=1.75; complex: OR=2.64), and prolonged postoperative hospital stays. CONCLUSIONS: We depicted the incidence of challenging separation from CPB among cardiac surgery population. Additionally, results of influential factors and various adverse outcome analyses emphasize the potential of interventions aimed at preventing difficult or complex separation from CPB and reducing associated adverse outcomes.

A comprehensive review on the documented characteristics of four Reticulitermes termites (Rhinotermitidae, Blattodea) of China / Uma revisão abrangente sobre as características documentadas de quatro cupins Reticulitermes da China

Termites are known as social insects worldwide. Presently in China 473 species, 44 genera and 4 families of termites have been reported. Of them, 111 Reticulitermes species are widely spread in different zones of China. The dispersion flight season of these Chinese Reticulitermes species are usually started from February to June, but in some regions different species are distributed, sharing their boundaries and having overlapping flight seasons. These reasons become important sources of hybridization between two different heterospecific populations of termites. It was confirmed that the fertilized eggs and unfertilized eggs of some Reticulitermes termites have the capacity of cleavage. While the unfertilized eggs of R. aculabialis, R. chinensis and R. labralis cleaved normally and the only R. aculabialis unfertilized eggs develop in embryos. While, the R. flaviceps and R. chinensis were observed with their abnormal embryonic development, and not hatching of eggs parthenogenetically. They were reported more threatening to Chinese resources as they propagate with parthenogenesis, hybridization and sexual reproduction. Eggshell and macrophiles of eggs play important roles in species identification and control. Although, they are severe pests and cause a wide range of damages to wooden structures and products in homes, buildings, building materials, trees, crops, and forests in China's Mainland.

Os cupins são conhecidos como insetos sociais em todo o mundo. Atualmente na China foram relatadas 473 espécies, 44 gêneros e 4 famílias de cupins. Destas, 111 espécies de Reticulitermes estão amplamente distribuídas em diferentes zonas da China. A temporada de voo de dispersão dessas espécies chinesas de Reticulitermes geralmente começa de fevereiro a junho, mas em algumas regiões diferentes espécies são distribuídas, compartilhando seus limites e tendo temporadas de voo sobrepostas. Essas razões tornam-se importantes fontes de hibridização entre duas populações heteroespecíficas de cupins. Foi confirmado que os ovos fertilizados e não fertilizados de alguns cupins Reticulitermes possuem capacidade de clivagem. Já os ovos não fertilizados de R. aculabialis, R. chinensis e R. labralis clivaram normalmente, e os únicos ovos não fertilizados de R. aculabialis se desenvolvem em embriões. R. flaviceps e R. chinensis foram observados com desenvolvimento embrionário anormal, e não eclosão de ovos por partenogênese. Eles foram relatados como mais ameaçadores para os recursos chineses à medida que se propagam com partenogênese, hibridização e reprodução sexual. Casca de ovo e macrófilos de ovos desempenham papéis importantes na identificação e controle de espécies, embora sejam pragas graves e causem uma ampla gama de danos a estruturas e produtos de madeira em residências, edifícios, materiais de construção, árvores, plantações e florestas na China continental.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Use of Radiomics Models in Preoperative Grading of Cerebral Gliomas and Comparison with Three-dimensional Arterial Spin Labelling.

AIMS: To build machine learning-based radiomics models to discriminate between high- (HGGs) and low-grade gliomas (LGGs) and to compare the effectiveness of three-dimensional arterial spin labelling (3D-ASL) to evaluate which is a better method. MATERIALS AND METHODS: We retrospectively analysed the magnetic resonance imaging T1WI-enhanced images of 105 patients with gliomas that were pathologically confirmed in our hospital. We divided the patients into a training group and a verification group at a ratio of 8:2; 200 patients from the Brain Tumour Segmentation Challenge 2020 were selected as the test group for image segmentation, feature extraction and screening. We constructed models using multilayer perceptron (MLP), support vector machine, random forest and logistic regression and evaluated their predictive performance. We obtained the mean maximum relative cerebral blood flow (rCBFmax) value from 3D-ASL of 105 patients from the hospital to evaluate its efficacy in discriminating between HGGs and LGGs. RESULTS: In machine learning, the MLP classifier model exhibited the best performance in discriminating between HGGs and LGGs; the areas under the curve obtained by MLP and rCBFmax were 0.968 versus 0.815 (verification group) and 0.981 versus 0.815 (test group), respectively. The machine learning-based MLP classifier model performed better in discriminating between HGGs and LGGs than 3D-ASL. CONCLUSION: In our study, we found that machine learning-based radiomics models and 3D-ASL were valuable in discriminating between HGGs and LGGs and between them, the machine learning-based MLP model had better diagnostic performance.

An integrated 3D printed radioluminescent-based phantom for quality assurance on a robotic-arm linac.

Objective. To develop, characterize and improve upon a high-resolution 3D printed radioluminescence-based imaging phantom for quality assurance (QA) of a robotic arm linear accelerator.Approach. A phantom was constructed which consisted of a scintillating sheet, fiducial markers, a low-cost complementary metal-oxide semiconductor camera and a 3D printed light-tight enclosure. The camera, equipped with a 12 mm lens, was angled 45 degrees from the horizontal axis with a direct line of sight of the scintillating sheet. A perspective image transformation with optical distortion correction was employed to obtain beam's eye view images for different collimators. Beam profiles, Iris™ field size, multileaf collimator leaf positioning and central laser-radiation field coincidence QA tests were performed and compared against data obtained with gafchromic film. The phantom's short-term stability, sensitivity to changes in output, field size and leaf positioning were also assessed.Main Results. The limiting resolution of the optical system was measured to be ∼0.26 mm. Field size, as measured by the radioluminescence system for Iris apertures, agreed to within 0.2 mm of the values measured using film. The imaging system was sensitive to field size changes well below 0.2 mm and output changes as small as 1 monitor unit (MU). For the optical setup, the mean leaf deviation error for banksX1 andX2 was 0.21 and 0.17 mm at 800 mm source to axis distance, whereas the mean difference for the film dataset was 0.16 mm and 0.22 mm for banksX1 andX2, respectively. The optical system was able to detect leaf positioning errors as small as 0.2 mm. Compared with film data, excellent agreement was seen for relative central axis beam profiles for 10 mm and 5 mm beams.Significance. The phantom presented here is an alternative to film and electronic portal imager devices, due to its low-cost, portability, and high spatial and temporal resolution.

A comprehensive review on the documented characteristics of four Reticulitermes termites (Rhinotermitidae, Blattodea) of China.

Termites are known as social insects worldwide. Presently in China 473 species, 44 genera and 4 families of termites have been reported. Of them, 111 Reticulitermes species are widely spread in different zones of China. The dispersion flight season of these Chinese Reticulitermes species are usually started from February to June, but in some regions different species are distributed, sharing their boundaries and having overlapping flight seasons. These reasons become important sources of hybridization between two different heterospecific populations of termites. It was confirmed that the fertilized eggs and unfertilized eggs of some Reticulitermes termites have the capacity of cleavage. While the unfertilized eggs of R. aculabialis, R. chinensis and R. labralis cleaved normally and the only R. aculabialis unfertilized eggs develop in embryos. While, the R. flaviceps and R. chinensis were observed with their abnormal embryonic development, and not hatching of eggs parthenogenetically. They were reported more threatening to Chinese resources as they propagate with parthenogenesis, hybridization and sexual reproduction. Eggshell and macrophiles of eggs play important roles in species identification and control. Although, they are severe pests and cause a wide range of damages to wooden structures and products in homes, buildings, building materials, trees, crops, and forests in China's Mainland.

Mesenchymal Stem Cells Enhance Chemotaxis of Activated T Cells through the CCL2-CCR2 Axis In Vitro.

Activation and migration of donor T cells to the host target organs are critical mechanisms in the pathogenesis of graft-versus-host disease (GVHD). The role of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor CCR2 in the recruitment of T cells during immune or inflammatory response is also well known. For elucidation of the mechanism of the therapeutic effect of human bone marrow derived-mesenchymal stem cells (MSC) in GVHD, we studied the effect of these cells on migration of activated donor T cells through the CCL2-CCR2 axis in vitro. MSC were expanded from donors' bone marrow mononuclear cells. After co-culturing of IL-2-activated T cells with allogeneic MSC at different ratios, the levels of CCL2 in supernatants were measured by ELISA, and CCR2 expression in CD4+/CD8+ T cells subsets were detected by flow cytometry. The effect of MSC on the migration of activated T cells in the Transwell system was studied in the absence or presence of CCL2. Our results show that CCL2 levels in supernatants of co-cultures were significantly higher than in MSC monoculture and this increase depended on the number of MSC. MSC inhibited proliferation of T cells, but did not change the percentages of CD4+ and CD8+ T cells subsets. MSC can up-regulate the CCR2 expression in CD8+ subsets rather than in CD4+ subsets; MSC enhanced migration of IL-2-activated T cells to CCL2 by increasing the expression of CCR2. The data demonstrate that MSC can enhance chemotaxis of cytokine-activated T cells through the CCL2-CCR2 axis in vitro.

[Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma].

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

[Expression of RUNX2/LAPTM5 in MC3T3-E1 osteoblastic cells with induced mineralization].

OBJECTIVE: To investigate the association of the expressions of RUNX2/LAPTM5 with osteogenesis and lysosomes in osteoblastic cells during mineralization induction. METHODS: MC3T3- E1 cells cultured in osteogenic induction medium was examined for mineralization and osteogenic differentiation using Alizarin red staining and alkaline phosphatase (ALP) staining, respectively. RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of Runx2 and LAPTM5 in the cells during osteogenic induction for 5 days. The effects of overexpression and interference of RUNX2/ LAPTM5 on the expressions of ALP and osteocalcin (OCN) in the cells were examined with Western blotting. RESULTS: MC3T3- E1 cells cultured in osteogenic induction medium showed an increased number of mineralized nodules over time, and the size of the mineralized nodules increased as the culture time extended; the number of purple-blue granules stained by ALP also increased gradually with time. RT-qPCR and Western blotting showed that the expressions of RUNX2 and LAPTM5 in the cells increased progressively during osteogenic mineralization (P < 0.001). Overexpression and interference of RUNX2 obviously affected LAPTM5 expression in the cells (P < 0.05); modulation of LAPTM5 expression did not significantly affect RUNX2 expression but caused significant changes in ALP and OCN expressions (P < 0.01). CONCLUSION: RUNX2 /LAPTM5 may participate in the regulation of osteoblast differentiation, and RUNX2 may be involved in the regulation of LAPTM5 expression. RUNX2 /LAPTM5 may play a mediating role in the process of osteogenic mineralization involving lysosomes.

[Artificial Intelligence in epidemiology]. / Apports de l'Intelligence Artificielle en épidémiologie.

Artificial Intelligence can be leveraged to analyze great amounts of data. It can be used on images or textual data to define the epidemiology of diseases, such as cancer. In this review, we will present and discuss the applications of AI in this setting.

The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization.

OBJECTIVE: Osteoarthritis (OA) is characterized by articular cartilage loss, associated with synovial inflammation. We recently reported increased pro-inflammatory macrophages in murine post-traumatic OA (PTOA) joints, and blockade of the ubiquitin-proteasome system alleviates PTOA progression. However, the mechanisms whereby protein ubiquitination influences PTOA pathology are not well studied. We hypothesized that loss of the negative regulator of inflammation, E3 ligase Itch, in macrophages contributes to joint OA tissue damage by promoting pro-inflammatory polarization of macrophages. METHODS: Mice deficient Itch in macrophages (MΔItch) were generated by crossing Itchfl/fl mice with LysM-Cre mice. PTOA surgery was performed on global Itch knockout, Itch-/-, mice and MΔItch mice. Joint tissue damage and synovial macrophages were examined. Itch-/- cells were treated with IL-1 and pro-inflammatory polarization was determined. Expression of Itch protein and mRNA in PTOA synovium were assessed at different time points post PTOA. RESULTS: Similar to Itch-/- mice, MΔItch mice developed more severe joint damage than control mice following PTOA surgery (mean difference of OARSI score: 1.17 (95% CI 0.31-2.03) between MΔItch and Itchfl/fl mice), accompanied by increased the inflammatory macrophage infiltration in the synovium (mean difference of % F4/80 + CD86 + CD36-inflammatory macrophages: 14.81 (95% CI 8.90-20.73) between MΔItch and Itchfl/fl mice). Itch-/- macrophages exerted pro-inflammatory phenotype in response to IL-1ß treatment. Itch protein, but not mRNA levels decreased during PTOA progression. CONCLUSION: The negative regulator of inflammation, Itch, limits PTOA progression by inhibiting macrophage pro-inflammatory polarization. Itch protein degradation may contribute to PTOA pathology.

LncRNA NR2F1-AS1 promotes proliferation and metastasis of ESCC cells via regulating EMT.

OBJECTIVE: The aim of this study was to explore the expression of long non-coding ribonucleic acid (lncRNA) nuclear receptor subfamily 2 group F member 1-antisense RNA 1 (NR2F1-AS1) in esophageal squamous cell carcinoma (ESCC) tissues and cells and to investigate its effects on ESCC proliferation and metastasis. PATIENTS AND METHODS: The expression level of NR2F1-AS1 in 51 pairs of ESCC tissues and corresponding adjacent tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Meanwhile, NR2F1-AS1 expression in ESCC cells was measured via qRT-PCR as well. Subsequently, specific interference sequences of NR2F1-AS1 were designed, synthesized, and transiently transfected into ESCC cells. 48 h later, qRT-PCR assay was performed to detect the interference efficiency. The effects of small interfering (si)-NR2F1-AS1 on the proliferation of ESCC cells were determined through cell counting kit-8 (CCK-8) and colony formation assay. Wound healing and transwell assays were conducted to investigate the influences of si-NR2F1-AS1 on the migration and invasion of ESCC cells. Additionally, the changes in the expressions of epithelial-mesenchymal transition (EMT) molecular markers were detected by Western blotting. RESULTS: QRT-PCR assay revealed that the expression level of NR2F1-AS1 was significantly up-regulated in 42 of 51 cases of ESCC tissues (42/51, 82.4%). Compared with esophageal mucosal epithelial HET-1A cells, NR2FA-AS1 was highly expressed in ESCC cells. CCK-8 and colony formation assay indicated that the proliferation of ESCC cells decreased remarkably after interference in NR2F1-AS1 expression. The results of wound healing and transwell assays showed that the migration and metastasis of cells were significantly lower in si-NR2F1-AS1 group than those in si-NC group. Western blotting demonstrated that the expressions of EMT molecular markers were changed after interfering with NR2F1-AS1 expression. CONCLUSIONS: NR2F1-AS1 was highly expressed in ESCC tissues and cells. Furthermore, high expression of NR2F1-AS1 promoted the proliferation and metastasis of ESCC cells by modulating EMT.