Cancer-associated fibroblast infiltration in osteosarcoma: the discrepancy in subtypes pathways and immunosuppression.

Introduction: Osteosarcoma (OS), the primary malignant bone tumor, has a low survival rate for recurrent patients. Latest reports indicated that cancer-associated fibroblasts (CAFs) were the main component of tumor microenvironment, and would generate a variable role in the progression of tumors. However, the role of CAFs is still few known in osteosarcoma. Methods: The processed RNA-seq data and the corresponding clinical and molecular information were retrieved from the Cancer Genome Atlas Program (TCGA) database and processed data of tumor tissue was obtained from Gene Expression Omnibus (GEO) database. Xcell method was used in data processing, and Gene set variation analysis (GSVA) was used to calculates enrichment scores. Nomogram was constructed to evaluate prognostic power of the predictive model. And the construction of risk scores and assessment of prognostic predictive were based on the LASSO model. Results: This study classified Cancer Genome Atlas (TCGA) cohort into high and low CAFs infiltrate phenotype with different CAFs infiltration enrichment scores. Then TOP 9 genes were screened as prognostic signatures among 2,488 differentially expressed genes between the two groups. Key prognostic molecules were CGREF1, CORT and RHBDL2 and the risk score formula is: Risk-score = CGREF1*0.004 + CORT*0.004 + RHBDL2*0.002. The signatures were validated to be independent prognostic factors to predict tumor prognosis with single-factor COX and multi-factor COX regression analyses and Norton chart. The risk score expression of risk score model genes could predict the drug resistance, and significant differences could be found between the high and low scoring groups for 17-AAG, AZD6244, PD-0325901 and Sorafenib. Discussion: To sum up, this article validated the prediction role of CAF infiltration in the prognosis of OS, which might shed light on the treatment of OS.

Progress of research on tumor organoids: A bibliometric analysis of relevant publications from 2011 to 2021.

Background: Research on tumor organoids has developed rapidly over the past 20 years, but a systematic analysis of current research trends is lacking. Researchers in the field need relevant references and knowledge of current research hot spots. Bibliometric analysis and visualization is a systematic method of acquiring an in-depth understanding of the status of research on tumor organoids. Methods: CiteSpace, VOSviewer and the Bibliometric Online Analysis Platform from the Web of Science Core Collection were used to analyze and predict publishing trends and research hot spots worldwide in the field of tumor organoids. Results: A total of 3,666 publications on tumor organoids were retrieved, and 2,939 eligible articles were included in the final analysis. The number of publications has grown significantly, with the United States of America as the leading country for research on tumor organoids. Among journals, Cancers published the largest number of articles. Harvard Medical School published the highest number of articles among all institutions. The Chinese Academy of Sciences was ranked highest among all contributing institutions on the importance of their publications. A trend in multi-disciplinary collaboration was observed in studies on tumor organoids. Keywords indicated that the current research largely concentrated on optimizing the construction of organoid models to use for medication development and screening in the clinical setting, and to provide patients with individualized treatment for gastric cancer and colorectal cancer, which are newly emerging research hotspots. Gastric and colorectal cancers were the top two tumors that have received increasing attention and have become the focal points of recent studies. Conclusion: This study analyzed 2,939 publications covering the topic of tumor organoids. Although optimizing the construction of organoid models has always been a hot topic in this field, the application of tumor organoids to the development of medications and screenings will foster individualized treatment for patients, which is another emerging hot spot in this field of research.

Polypyrrole coated carbon nanotube aerogel composite phase change materials with enhanced thermal conductivity, high solar-/electro- thermal energy conversion and storage.

Phase change materials (PCMs) have been widely investigated as promising thermal management materials due to their high thermal storage capacity, satisfactory heat transfer rate and multi-responsive energy conversion and storage characteristics. In this work, a shape-stabilized solar-/electro- responsive thermal energy capture and storage system is proposed involving polypyrrole (PPy)-deposited carbon nanotubes (CNT) heterogeneous porous aerogel as a supporting matrix and the paraffin wax (PW) as a PCM. The composite PCMs obtained via integration of PW into aerogel supports present a relatively high thermal storage density of 160.9 J/g and outstanding phase transition stability even after 100 heating-cooling cycles. Furthermore, great enhancement of thermal conductivity (0.64 W/m-1·K-1, 2.56 times that of PW) is achieved in the composite PCMs by inducing PPy coating as a binder in the gap between CNTs. The mechanism of heat transport enhancement is explored by molecular dynamics simulation. It concludes that the in-situ polymerization of PPy through the vapor deposition method on the CNT aerogels effectively builds additional thermal transfer channels and enhances the heat transport between CNT by coordinating the carbon atom vibration. Herein, this reported stratagem may shed light on preparing composite PCMs with high thermal conductivity and multi-energy utilization functions.

Recent advances of eosinophils and its correlated diseases.

Eosinophils are differentiated by bone marrow multipotent progenitor cells and are further released into peripheral blood after maturation. Human eosinophils can exhibit unique multi-leaf nuclear morphology, which are filled with cytoplasmic granules that contain cytotoxicity and immune regulatory proteins. In recent years, many studies focused on the origin, differentiation and development process of eosinophils. It has been discovered that the eosinophils have the regulatory functions of innate and adaptive immunity, and can also function in several diseases, including asthma, chronic obstructive pulmonary diseases, acute respiratory distress syndrome, malignant tumors and so on. Hence, the role and effects of eosinophils in various diseases are emphasized. In this review, we comprehensively summarized the development and differentiation process of eosinophils, the research progress of their related cytokines, diseases and current clinical treatment options, and discussed the potential drug target, aiming to provide a theoretical and practical basis for the clinical prevention and treatment of eosinophil-related diseases, especially respiratory diseases. To conclude, the guiding significance of future disease treatment is proposed based on the recent updated understandings into the cell functions of eosinophils.

Comparison of Short-Term Restorative Effects and Periodontal Health Status of Restorations Made of Different Materials in Full-Crown Restoration of Mandibular Premolar Tooth Defects.

Purpose: To compare the short-term restorative effect and periodontal health status of restorations with different materials in full-crown restoration of mandibular premolar tooth defects. Methods: A total of 105 cases (123 affected teeth) of mandibular premolar tooth defects who visited the Department of Stomatology between January 2019 and January 2020 were selected, of which 58 cases (68 affected teeth) restored with cobalt-chromium alloy porcelain crowns were included in the metal-ceramic crown (MCC) group and 47 cases (55 affected teeth) repaired by zirconium dioxide all-ceramic crowns were assigned to the zirconia crown (ZC) group. The restorative effect, inflammatory factors (high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α)) and periodontal health indicators (human cartilage glycoprotein-39 (YKL-40), resistin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) after treatment, and the occurrence of adverse reactions were compared between the two groups. Results: The ZC group outperformed the MCC group in terms of margin fitness, restoration fracture, gingival condition, and color matching. After restoration, hs-CRP and TNF-α were statistically decreased in both groups, while YKL-40, resistin, AST, and ALP were significantly increased; and compared with the MCC group, hs-CRP, TNF-α, YKL-40, resistin, AST, and ALP were lower in the ZC group. The ZC group also scored statistically higher in retention effect, aesthetic effect, masticatory function, voice function, and comfort. Moreover, the ZC group had a higher total effective rate and a lower incidence of adverse reactions than the MCC group, with statistical significance. Conclusions: Zirconia dioxide all-ceramic crowns contribute to a better short-term restorative effect in the full-crown restoration of mandibular premolar tooth defects, with little impact on periodontal health and high patient satisfaction, which deserves popularization and application.

Combination of chemotherapy and immune checkpoint therapy by the immunoconjugates-based nanocomplexes synergistically improves therapeutic efficacy in SCLC.

Although the etoposide and carboplatin (EP) combination strategy has been the first-line chemotherapy, patients with extensive-stage disease small-cell lung cancer (SCLC) still have poor survival outcomes. Our retrospective analysis revealed that 46 patients with SCLC only achieved medium overall survival (OS) of 11.6 months after treated by EP. Recently, it was demonstrated that combination therapy of PD1/PD-L1 immune checkpoint blocker and EP could significantly improve the OS of SCLC patients. However, the serious treatment-related toxicity leaded to a high rate of treatment-discontinuation or even death. In the present study, we have developed a novel TPP1-conjugated nanocomplex, abbreviated as TPP1NP-EP, which was co-loaded with carboplatin (CBP) and etoposide (VP16). The TPP1 was a PD-L1 targeting peptide and conjugated on the surface of nanocomplex by a matrix metalloproteinase (MMP-2/9)-cleavable peptide linker sequence PLGLAG. For dual-loading of CBP and VP16, the CBP was chemically conjugated with poly(ethylene glycol) (PEG)-poly(caprolactone) (PCL) by pH-sensitive hydrazone bond and the VP16 was physically encapsulated by emulsion-solvent evaporation method. In vitro and in vivo experiments demonstrated an excellent anti-tumor effect of TPP1NP-EP on SCLC and improved safety. In conclusion, the present study has provided a promising strategy for treatment of malignant SCLC.

Artificial intelligence-based assessments of colonoscopic withdrawal technique: a new method for measuring and enhancing the quality of fold examination.

BACKGROUND: This study aimed to develop an artificial intelligence (AI)-based system for measuring fold examination quality (FEQ) of colonoscopic withdrawal technique. We also examined the relationship between the system's evaluation of FEQ and FEQ scores from experts, and adenoma detection rate (ADR) and withdrawal time of colonoscopists, and evaluated the system's ability to improve FEQ during colonoscopy. METHODS: First, we developed an AI-based system for measuring FEQ. Next, 103 consecutive colonoscopies performed by 11 colonoscopists were collected for evaluation. Three experts graded FEQ of each colonoscopy, after which the recorded colonoscopies were evaluated by the system. We further assessed the system by correlating its evaluation of FEQ against expert scoring, historical ADR, and withdrawal time of each colonoscopist. We also conducted a prospective observational study to evaluate the system's performance in enhancing fold examination. RESULTS: The system's evaluations of FEQ of each endoscopist were significantly correlated with experts' scores (r = 0.871, P < 0.001), historical ADR (r = 0.852, P = 0.001), and withdrawal time (r = 0.727, P = 0.01). For colonoscopies performed by colonoscopists with previously low ADRs (< 25 %), AI assistance significantly improved the FEQ, evaluated by both the AI system (0.29 [interquartile range (IQR) 0.27-0.30] vs. 0.23 [0.17-0.26]) and experts (14.00 [14.00-15.00] vs. 11.67 [10.00-13.33]) (both P < 0.001). CONCLUSION: The system's evaluation of FEQ was strongly correlated with FEQ scores from experts, historical ADR, and withdrawal time of each colonoscopist. The system has the potential to enhance FEQ.

M2 macrophagy-derived exosomal miRNA-26a-5p induces osteogenic differentiation of bone mesenchymal stem cells.

BACKGROUND: Bone marrow mesenchymal stem cells have always been a heated research topic in bone tissue regeneration and repair because of their self-renewal and multi-differentiation potential. A large number of studies have been focused on finding the inducing factors that will promote the osteogenic differentiation of bone marrow mesenchymal stem cells. Previous studies have shown that macrophage exosomes or miRNA-26a-5p can make it work, but the function of this kind of substance on cell osteogenic differentiation has not been public. METHODS: M2 macrophages are obtained from IL-4 polarized bone marrow-derived macrophages. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), western blotting, and DLS. Chondrogenic differentiation potential was detected by Alcian blue staining. Oil red O staining was used to detect the potential for lipogenic differentiation. And MTT would detect the proliferative capacity of cells. Western blot was performed to detect differential expression of osteogenic differentiation-related proteins. RESULTS: The results showed that M2 macrophage exosomes will promote bone differentiation and at the same time inhibit lipid differentiation. In addition, M2 macrophage-derived exosomes have the function of promoting the expression of SOX and Aggrecan suppressing the level of MMP13. The exosome inhibitor GW4689 suppresses miRNA-26a-5p in M2 macrophage exosomes, and the treated exosomes do not play an important role in promoting bone differentiation. Moreover, miRNA-26a-5p can enable to promote bone differentiation and inhibit lipid differentiation. miRNA-26a-5p can promote the expression of ALP (alkaline phosphatase), RUNX-2 (Runt-related transcription factor 2), OPN(osteopontin), and Col-2(collagen type II). Therefore, it is speculated that exosomal miRNA-26a-5p is indispensable in osteogenic differentiation. CONCLUSIONS: The present study indicated that M2 macrophage exosomes carrying miRNA-26a-5p can induce osteogenic differentiation of bone marrow-derived stem cells to inhibit lipogenic differentiation, and miRNA-26a-5p will also promote the expression of osteogenic differentiation-related proteins ALP, RUNX-2, OPN, and Col-2.

A deep learning-based dual-omics prediction model for radiation pneumonitis.

PURPOSE: Radiation pneumonitis (RP) is the main source of toxicity in thoracic radiotherapy. This study proposed a deep learning-based dual-omics model, which aims to improve the RP prediction performance by integrating more data points and exploring the data in greater depth. MATERIALS AND METHODS: The bimodality data were the original dose (OD) distribution and the ventilation image (VI) derived from four-dimensional computed tomography (4DCT). The functional dose (FD) distribution was obtained by weighting OD with VI. A pre-trained three-dimensional convolution (C3D) network was used to extract the features from FD, VI, and OD. The extracted features were then filtered and selected using entropy-based methods. The prediction models were constructed with four most commonly used binary classifiers. Cross-validation, bootstrap, and nested sampling methods were adopted in the process of training and hyper-tuning. RESULTS: Data from 217 thoracic cancer patients treated with radiotherapy were used to train and validate the prediction model. The 4DCT-based VI showed the inhomogeneous pulmonary function of the lungs. More than half of the extracted features were singular (of none-zero value for few patients), which were eliminated to improve the stability of the model. The area under curve (AUC) of the dual-omics model was 0.874 (95% confidence interval: 0.871-0.877), and the AUC of the single-omics model was 0.780 (0.775-0.785, VI) and 0.810 (0.804-0.811, OD), respectively. CONCLUSIONS: The dual-omics outperformed single-omics for RP prediction, which can be contributed to: (1) using more data points; (2) exploring the data in greater depth; and (3) incorporating of the bimodality data.

Xi Lei San Attenuates Dextran Sulfate Sodium-Induced Colitis in Rats and TNF-α-Stimulated Colitis in CACO2 Cells: Involvement of the NLRP3 Inflammasome and Autophagy.

OBJECTIVE: Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory bowel disease with an unclear etiology. The active ingredients of traditional Chinese medicines (TCMs) exert anti-inflammatory, antitumor, and immunomodulatory effects, and their multitarget characteristics provide them with a unique advantage for treating IBD. However, the therapeutic effects and underlying mechanisms of Xi Lei San in treatment of IBD remain unknown. This study was designed to investigate whether Xi Lei San exerted an anti-inflammatory effect in IBD via a mechanism involving NLRP3 inflammasomes and autophagy. METHODS: We successfully established a rat model of dextran sulfate sodium- (DSS-) induced colitis as well as a cellular model of TNF-α-induced colitis. Xi Lei San and indirubin were identified by HPLC analysis. Rats were treated with Xi Lei San or alum crystals, and their body weights and morphology of intestinal tissues were examined. A western blot analysis was performed to determine the expression levels of inflammasome-related proteins and autophagy-related proteins, ELISA was performed to analyze IL-1ß, IL-18, and IL-33 concentrations, and flow cytometry was used to monitor cell apoptosis and ROS levels. RESULTS: Xi Lei San and indirubin were identified by HPLC analysis. We found that Xi Lei San could significantly increase the weights of rats and improve the structure of the intestinal tissues in DSS-induced colitis model rats. We also found that Xi Lei San significantly inhibited NLRP3 inflammasome activity, reduced the levels of inflammatory cytokines, and suppressed autophagy in DSS-induced colitis model rats. In vitro experiments revealed that Xi Lei San could repress apoptosis as well as ROS and inflammatory cytokine production in TNF-α-induced CACO2 cells by reducing the activity of NLRP3 inflammasomes and autophagy. CONCLUSIONS: Our findings showed that Xi Lei San significantly ameliorated IBD by inhibiting NLRP3 inflammasome, autophagy, and oxidative stress.

Fuzheng Huayu Capsule Attenuates Hepatic Fibrosis by Inhibiting Activation of Hepatic Stellate Cells.

AIM: To investigate the mechanisms of Fuzheng Huayu (FZHY) Capsule in the treatment of hepatitis B (HBV)- associated fibrosis, HBV patients were divided into two groups, 50 cases were in the nucleotide analogues (NAs) group, while additional 50 cases were in the NAs + FZHY group. METHODS: We assessed the curative effects of antifibrosis through liver function, FibroScan test, and liver biopsy and detected the ratio of lymphocyte subsets by flow cytometry. Peripheral blood lymphocyte and CD8+T, CD4+T, and natural killer cell subsets collected from patients were cocultured with LX-2 cells. Activation of LX-2 cells, production of the extracellular matrix, apoptosis, and proliferation of LX-2 cells were determined. Chronic liver injury models were established by ConA treatment. RESULTS: It is evident that FZHY treatment significantly increased the percentage of NK cells, the rate of death, and apoptosis of LX-2 cells and decreased the FibroScan liver stiffness measurement value. The expressions of α-SMA and procollagen type I mRNA in LX-2 cells of the FZHY treatment group as downregulated when they were cocultured with lymphocytes compared to those from the NAs group. The proliferation of LX-2 cells in the FZHY treatment group was inhibited compared to that in the NAs group. In a mouse model of hepatic fibrosis, PBLs and IHLs from ConA exposure plus FZHY treatment inhibited the ability of JS-1 cells to express α-SMA. CONCLUSIONS: FZHY Capsule improved the disordered cellular immunity and postponed liver fibrosis possibly through inhibiting the interaction between lymphocyte and hepatic stellate cells.

Clinical impact of cardiovascular disease on patients with bronchiectasis.

BACKGROUND: Patients with bronchiectasis have a higher cardiovascular risk than their matched controls. However, the effect of cardiovascular (CV) disease on bronchiectasis remains unclear. Thus, we aimed to investigate the clinical impacts of cardiovascular disease on adult patients with bronchiectasis. METHODS: The study cohort comprised 603 consecutive inpatients diagnosed with bronchiectasis in the Affiliated Yancheng Hospital of Southeast University Medical College (Jiangsu, China) from January 2014 to December 2017. Symptoms, bacterial cultures, blood biochemical indicator levels, and chest high-resolution computed tomography scans were assessed during their initial hospitalization for bronchiectasis. Three hundred and thirty five subjects finished 1 year follow-up after their hospital discharge. RESULTS: Three hundred thirty five patients had at least one bronchiectasis exacerbation during the 1-year follow-up period. Patients with CV comorbidities were more likely to present with symptoms of wheezing (65.3%) and had a higher levels of brain natriuretic peptide (P < 0.001) and D-dimer (P < 0.001) than those without CV comorbidities. Independent risk factors associated with bronchiectasis exacerbations were the presence of comorbidities of cardiovascular diseases (odds ratio [OR] 2.503, 95% confidence interval [CI] 1.298-4.823; P = 0.006), the isolation of Pseudomonas aeruginosa (OR 2.076, 95% CI 1.100-3.919; P = 0.024), and extension to more than two lobes (OR 2.485, 95% CI 1.195-5.168; P = 0.015). CONCLUSION: The existence of cardiovascular disease was independently associated with increased bronchiectasis exacerbation.

Three Cases of Brucellar Spondylitis with Noncontiguous Multifocal Involvement.

BACKGROUND: Brucellosis is an endemic disease. Brucellar spondylitis is mainly manifested as a unifocal lesion, but noncontiguous multifocal brucellar spondylitis is more rare. CASE DESCRIPTION: Herein, we report 3 patients with noncontiguous multifocal involvement of brucellar spondylitis who are over 51 years of age. The diagnosis was established by using magnetic resonance imaging (MRI) and positive brucellar agglutination test. All patients were cured with antibrucellosis chemotherapy and surgery. For patients with a high degree of suspicion of noncontiguous multifocal brucellar spondylitis, especially elderly patients, screening with the use of serologic test for brucellosis and whole spine MRI is crucial to reduce the rate of misdiagnosis and missed diagnosis. CONCLUSIONS: Clinicians should raise awareness of noncontiguous multifocal brucellar spondylitis. The Wright agglutination test and whole spine MRI are the key methods to reduce misdiagnosis and missed diagnosis of noncontiguous multifocal brucellar spondylitis. Drug therapy for brucellar spondylitis is the basis, and surgical treatment is complementary therapy. The use of alternative chemotherapy and surgery for noncontiguous multifocal brucellar spondylitis is also safe and effective.

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis.

Osteoarthritis, a disorder characterized by articular cartilage deterioration, varying degrees of inflammation, and chondrocyte apoptosis, is the most common chronic joint disease. To slow or reverse its progression, inflammation should be inhibited, and chondrocyte proliferation should be promoted. Tetrahedral framework nucleic acids can be internalized by chondrocytes (even inflammatory chondrocytes) and can enhance their proliferation and migration. Wogonin, a naturally occurring flavonoid, suppresses oxidative stress and inhibits inflammation. In this study, tetrahedral framework nucleic acids were successfully self-assembled and used to load wogonin. We confirmed the effective formation of tetrahedral framework nucleic acid/wogonin complexes by dynamic light scattering, zeta potential analysis, transmission electron microscopy, and fluorescence spectrophotometry. Tetrahedral framework nucleic acids, wogonin, and especially tetrahedral framework nucleic acid/wogonin complexes effectively alleviated inflammation in vitro and in vivo and prevented cartilage destruction. In addition, these materials remarkably downregulated the expression of inflammatory mediators and matrix metalloproteinases, upregulated chondrogenic markers, and promoted tissue inhibitor of metalloproteinase 1 and B-cell lymphoma 2 expression. In vivo, after treatment with tetrahedral framework nucleic acid/wogonin complexes, the bone mineral density in regenerated tissues was much higher than that found in the untreated groups. Histologically, the complexes enhanced new tissue regeneration, significantly suppressed chondrocyte apoptosis, and promoted chondrogenic marker expression. They also inhibited cell apoptosis, increased chondrogenic marker expression, and suppressed the expression of inflammatory mediators in osteoarthritis. Therefore, we believe that tetrahedral framework nucleic acid/wogonin complexes can be used as an injectable form of therapy for osteoarthritis.