Receptor tyrosine kinases in breast cancer treatment: unraveling the potential.

Breast cancer is a multifactorial disease driven by acquired genetic and epigenetic changes that lead to aberrant regulation of cellular signaling pathways. Receptor tyrosine kinases (RTKs), a class of critical receptors, are involved in the initiation and progression of breast cancer. RTKs are cell surface receptors with unique structures and biological characteristics, which respond to environmental signals by initiating signaling cascades such as the mitogen-activated protein kinase (MAPK) pathway, Janus kinase (JAK)/signal transducer, activator of transcription (STAT) pathway, and phosphoinositide 3-kinase (PI3K)/AKT pathway. The critical role of RTKs makes them suitable targets for breast cancer treatment. Targeted therapies against RTKs have been developed in recent years, evaluated in clinical trials, and approved for several cancer types, including breast cancer. However, breast cancer displays molecular heterogeneity and exhibits different therapeutic responses to various drug types, leading to limited effectiveness of targeted therapy against RTKs. In this review, we summarize the structural and functional characteristics of selected RTKs and discuss the mechanisms and current status of drug therapy involving different protein tyrosine kinases in breast cancer progression.

Integrating Lysosomal Genes and Immune Infiltration for Multiple Myeloma Subtyping and Prognostic Stratification.

Lysosomes are crucial in the tumour immune microenvironment, which is essential for the survival and homeostasis in multiple myeloma (MM). Here, we aimed to identify lysosome-related genes for the prognosis of MM and predicted their regulatory mechanisms. Gene expression profiles of MM from the GSE2658 and GSE57317 datasets were analysed. Lysosome-related differentially expressed genes (DEGs) were identified and used for molecular subtyping of MM patients. A prognostic model was constructed using univariate Cox regression and LASSO regression analyses. The relationship between prognostic genes, immune cell types, and autophagy pathways was assessed through correlation analysis. RT-qPCR was performed to validate the expression of prognostic genes in MM cells. A total of 9,954 DEGs were identified between high and low immune score groups, with 213 intersecting with lysosomal genes. Molecular subtyping revealed two distinct MM subtypes with significant differences in immune cell types and autophagy pathway activities. Five lysosome-related DEGs (CORO1A, ELANE, PSAP, RNASE2, and SNAPIN) were identified as significant prognostic markers. The prognostic model showed moderate predictive accuracy with AUC values up to 0.723. Prognostic genes demonstrated significant correlations with various immune cell types and autophagy pathways. Additionally, CORO1A, PSAP and RNASE2 expression was up-regulated in MM cells, while ELANE and SNAPIN were down-regulated. Five lysosomal genes in MM were identified, and a new risk model for prognosis was developed using these genes. This research could lead to discovering important gene markers for the treatment and prognosis of MM.

Immunogenic cell death (ICD) genes predict immunotherapy response and therapeutic targets in acute myeloid leukemia (AML).

Introduction: Numerous studies have demonstrated acute myeloid leukemia (AML) is one of the malignancies with high mortality worldwide. Immunogenic cell death (ICD) is a form of cell death that is specialised in that it triggers the body's immune response, particularly the adaptive immune response. Recent evidence has confirmed that pseudogenes are implicated in multiple human tumorigenesis and progression although lacking the function of coding protein. However, the roles of ICD-associated genes in AML remain largely unascertained. Methods: TCGA-AML and GSE71014 cohorts were picked out and we combined them into a merged dataset by removing the batch effect using the sva package in the R project. A consensus clustering analysis of the ICD genes in AML was performed to define subgroups. Based on the expression of 15 prognostic-related pseudogenes, we developed a prognostic model and categorized AML samples into low and high-risk groups. Results: AML was differentiated into two subgroups (C1 and C2 clusters). Most ICD-related genes were significantly up-regulated in the C2 cluster. The single sample gene set enrichment analysis (ssGSEA) revealed that the immune cell infiltration and immune checkpoint gene expression of the C2 cluster was strongly high, suggesting that the C2 population responded well to immune checkpoint blockade (ICB) therapy and had better survival. The C1 group was sensitive to chemotherapy, including Cytarabine, Midostaurin, and Doxorubicin. On the other hand, 15 ICD-related pseudogenes were identified to be associated with AML prognosis. The receiver operator curve (ROC) analysis and nomogram manifested that our prognostic model had high accuracy in predicting survival. However, the high-risk group was sensitive to ICB therapy and chemotherapy such as Methotrexate, Cytarabine, and Axitinib while the low-risk group benefited from 5-Fluorouracil, Talazoparib, and Navitoclax therapy. Discussion: In summary, we defined two subgroups relying on 33 ICD-related genes and this classification exerted a decisive role in assessing immunotherapy and chemotherapy benefit. Significantly, a prognostic signature identified by critical ICD-related pseudogene was created. The pseudogene prognostic signature had a powerful performance in predicting prognosis and therapeutic efficacy, including immunotherapy and chemotherapy to AML. Our research points out novel implications of ICD in cancer prognosis and treatment approach choice.

Lymph node myeloid sarcoma with TP53­associated myelodysplastic syndrome: A case report.

Myeloid sarcoma (MS) is a rare extramedullary tumor mass that carries a high risk of progression to acute myeloid leukemia (AML), and patients with MS are commonly treated with the AML regimen. However, MS is frequently misdiagnosed due to its lack of clinical specificity. Patients with MS who harbor tumor protein p53 (TP53) mutations and complex karyotypes are considered to have a poorer prognosis. The present study reports a case of lymph node MS with TP53 (V173G)-related myelodysplastic syndrome (MDS). The mass was first considered to be a lymphoma and treated as such. However, following immunohistochemical analysis, which revealed cells positive for CD43, myeloperoxidase and CD117, the patient was later diagnosed with MS combined with MDS. The patient went into complete remission after the first cycle of chemotherapy, and showed a decrease in platelet, red blood cell and white blood cell counts following the second cycle of chemotherapy. After the third chemotherapy, agranulocytosis occurred, leading to refractory pneumonia and eventually death due to respiratory failure. MS with TP53-related MDS has a low incidence rate, a poor prognosis and a short survival time. The clinical manifestations of MS are non-specific and easy to misdiagnose, leading to delayed diagnosis and treatment, and ultimately worsening the prognosis of the patients. Therefore, a lymph node biopsy should be performed as soon as possible for patients with lymph node enlargement, and early treatment should be carried out to prolong the survival period.

[Effects of plumbagin on proliferation and apoptosis of human hepatocellular carcinoma cells based on CKB/p53 signaling pathway].

To investigate the effects of plumbagin on the proliferation and apoptosis of human hepatoma Huh-7 cells and its mechanism based on the creatine kinase B(CKB)/p53 signaling pathway. Huh-7 cells were treated with plumbagin from 1 to 12 µmol·L~(-1) for cell counting kit-8(CCK-8) assay, and 1, 3, and 6 µmol·L~(-1) were determined as low, medium, and high concentrations of plumbagin for subsequent experiments. CKB gene was knocked out in Huh-7 cells by clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)-9 gene editing technology. CKB overexpression lentivirus was transfected into Huh-7 cells to up-regulate the expression of CKB. Cell proliferation and apoptosis were detected by plate cloning assay and flow cytometry. The mRNA expression of CKB was detected by quantitative real-time PCR(qRT-PCR). CKB, p53, mouse double minute 2 homolog(MDM2), B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), and caspase-3 protein were detected by Western blot(WB). The results showed that plumbagin significantly inhibited the proliferation of Huh-7 cells and induced cell apoptosis. Compared with the control group, the apoptosis level was significantly increased in the plumbagin group, while the apoptosis level was significantly decreased in the plumbagin combined with the apoptosis inhibitor group. Plumbagin significantly down-regulated the protein expression levels of CKB, Bcl-2, and MDM2 and up-regulated the protein expression levels of p53, Bax, and caspase-3. Knockdown of the CKB gene decreased the proliferative ability of Huh-7 cells, increased the apoptotic rate, decreased the expression levels of Bcl-2 and MDM2 proteins, and increased the expression levels of p53, Bax, and caspase-3 proteins. After up-regulation of CKB expression, the proliferation ability of Huh-7 cells was enhanced, and the protein expression levels of Bcl-2 and MDM2 were elevated. The protein expression levels of p53, Bax, and caspase-3 were decreased. In addition, plumbagin reversed the effect of overexpression of CKB on the proliferation and apoptosis of Huh-7 cells. In conclusion, plumbagin significantly inhibited the proliferative ability of Huh-7 cells, and the mechanism may be related to the inhibition of CKB expression, activation of the p53 signaling pathway, and regulation of the expression of mitochondrial-associated apoptotic proteins, ultimately inducing cell apoptosis.

Serum IL-24 combined with CA125 as screening and prognostic biomarkers for NSCLC.

Noninvasive and effective methods for early screening of non-small cell lung cancer (NSCLC) still need to be developed. At present, a reasonable conclusion is that a combination of tumor markers is a superior predictor of screening. Cytokines, as important regulators of cancer development, have great potential for the screening and prognosis of NSCLC. This study screened novel biomarkers related to the early screening and prognosis of NSCLC. In the present study, the biological significance and immunoregulation of interleukin-24 (IL-24) were analyzed based on The Cancer Genome Atlas data. Next, 150 serum samples from initially treated patients with NSCLC and 70 controls were collected, and we obtained pathological sections from 60 patients with NSCLC. The ELISA and immunohistochemistry results showed the differential expression of IL-24 and carbohydrate antigen 125 (CA125). The results show that IL-24 is an important tumor suppressor in NSCLC that helps to improve the poor prognosis of these patients. A significantly negative correlation between IL-24 and CA125 levels was also found. Notably, serum IL-24 levels were significantly negatively correlated with the TNM stage of patients with NSCLC, consistent with an important role for tumor suppressors in NSCLC. The receiver operating characteristic curve analysis showed that a combination of IL-24 and CA125 was an effective panel for discriminating patients with NSCLC from HD, and individuals with other lung diseases. Serum IL-24 and CA125 levels were identified as independent prognostic markers for NSCLC. The IL-24 and CA125 panel exhibited good performance in the screening of NSCLC.

Dexamethasone-Loaded Lipid Calcium Phosphate Nanoparticles Treat Experimental Colitis by Regulating Macrophage Polarization in Inflammatory Sites.

Background: The M1/M2 polarization of intestinal macrophages exerts an essential function in the pathogenesis of ulcerative colitis (UC), which can be adjusted to alleviate the UC symptoms. Purpose: A kind of pH-sensitive lipid calcium phosphate core-shell nanoparticles (NPs), co-loading with dexamethasone (Dex) and its water-soluble salts, dexamethasone sodium phosphate (Dsp), was constructed to comprehensively regulate macrophages in different states towards the M2 phenotype to promote anti-inflammatory effects. Methods: Dex and Dsp were loaded in the outer lipid shell and inner lipid calcium phosphate (Cap) core of the LdCaPd NPs, respectively. Then, the morphology of NPs and methods for determining drug concentration were investigated, followed by in vitro protein adsorption, stability, and release tests. Cell experiments evaluated the cytotoxicity, cellular uptake, and macrophage polarization induction ability of NPs. The in vivo distribution and anti-inflammatory effect of NPs were evaluated through a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced BALB/c mice ulcerative colitis model. Results: The LdCaPd NPs showed a particle size of about 200 nm and achieved considerable loading amounts of Dex and Dsp. The in vitro and in vivo studies revealed that in the acidic UC microenvironment, the cationic lipid shell of LdCaPd underwent protonated dissociation to release Dex first for creating a microenvironment conducive to M2 polarization. Then, the exposed CaP core was further engulfed by M1 macrophages to release Dsp to restrict the pro-inflammatory cytokines production by inhibiting the activation and function of the nuclear factor kappa-B (NF-κB) through activating the GC receptor and the NF kappa B inhibitor α (I-κBα), respectively, ultimately reversing the M1 polarization to promote the anti-inflammatory therapy. Conclusion: The LdCaPd NPs accomplished the sequential release of Dex and Dsp to the UC site and the inflammatory M1 macrophages at this site, promoting the regulation of macrophage polarization to accelerate the remission of UC symptoms.

Efficacy and Safety of Bilateral Ultrasound-Guided Erector Spinae Plane Block for Postoperative Analgesia in Spine Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: A meta-analysis of randomized controlled trials was conducted to assess efficacy and safety of bilateral ultrasound-guided erector spinae plane block (ESPB) for postoperative analgesia in patients receiving spine surgery. METHODS: PubMed, Embase, and CENTRAL databases were searched by 2 reviewers independently to identify randomized controlled trials evaluating the efficacy of ultrasound-guided ESPB for pain management in patients undergoing spine surgery. For meta-analysis, mean difference (MD) and 95% confidence interval (CI) were selected for continuous data, and risk ratio (RR) and 95% CI were selected for dichotomous variables. RESULTS: A total of 25 randomized controlled trials including 1917 patients (873 in ESPB group and 874 in control group) were eligible for inclusion. At rest, ESPB was associated with significantly lower pain intensity at 0, 2, 4, 6, 8, 12, 24, and 48 hours compared with the control group. During movement, ESPB was associated with significantly lower pain intensity at 0, 4, 6, 8, 12, 24, and 48 hours compared with the control group. Significantly reduced opioid consumption (MD = -6.29, 95% CI [-8.16, 4.41], P < 0.001), prolonged time for first rescue analgesia (MD = 7.51, 95% CI [3.47, 11.54], P < 0.001), fewer patients needing rescue analgesia (RR = 0.34, 95% CI [0.28, 0.43], P < 0.0001), improved patient satisfaction (MD = 1.34, 95% CI [0.88, 1.80], P < 0.001), and shorter length of hospital stay (MD = -0.38, [95% CI -0.50, -0.26], P < 0.001) were demonstrated after use of ESPB. Additionally, ESPB was associated with decreased risks of any adverse event (RR = 0.51, 95% CI [0.43, 0.60], P < 0.001) and postoperative nausea and vomiting events (RR = 0.39, 95% CI [0.31, 0.49], P < 0.001). CONCLUSIONS: Ultrasound-guided ESPB is an effective adjunctive technique with good tolerability for multimodal analgesia in management of pain in patients undergoing spine surgery.

Comparison of anti-thymocyte globulin-based immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation in patients with transfusion-dependent non-severe aplastic anaemia: a retrospective study from a single centre.

OBJECTIVES: The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA) pose significant clinical challenges. This study aims to compare the efficacy and long-term outcomes of the two treatments in TD-NSAA. METHODS: Patients who underwent ATG-based IST or allo-HSCT between July 2011 and December 2019 were reviewed. We gathered their clinical information, treatment response, survival data, and subsequently analysed the associated risk factors. RESULTS: A total of 97 TD-NSAA patients were reviewed, and 55 patients who underwent either ATG-based IST (n = 27) or allo-HSCT (n = 28) were enrolled. We observed a significant disparity in the 12-month overall response rate (ORR) (48.1% in IST vs 78.6% in HSCT, p < 0.05), but not in five-year overall survival (OS) and event-free survival (EFS). Multivariate Cox regression analysis identified the transfusion of ≥78.75 units of red blood cells (RBCs) as the sole independent risk factor for OS (HR: 17.04, p = 0.039) in the IST group. For the HSCT group, disease duration (DD) ≥20 months and transfusion of ≥78.75 units of RBCs predicted an adverse EFS. Frontline IST exhibited superior 12-month ORR (68.8% vs 18.2%, p = 0.018) and five-year EFS when compared to non-frontline. Patients with a DD ranging from 6 to 20 months displayed a better EFS (p = 0.016) in HSCT group than those in the ATG-based IST group. CONCLUSIONS: Prior treatment history, disease duration, and serum ferritin levels should be carefully weighed when making the choice between ATG-based IST and allo-HSCT for TD-NSAA.

The selection and timing of anti-thymocyte globulin (ATG)-based immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (allo-HSCT) present notable clinical challenges for individuals with transfusion-dependent non-severe aplastic anaemia (TD-NSAA).In terms of treatment outcomes, allo-HSCT exhibited a higher 12-month overall response rate (ORR) in comparison to ATG-based IST among TD-NSAA patients. Nevertheless, comparable rates of 5-year overall survival (OS) and event-free survival (EFS) were observed between the two therapeutic approaches.Several factors warrant consideration when deliberating between ATG-based IST and allo-HSCT for TD-NSAA. These factors include the patient's prior treatment history, disease duration, number of packed red cell transfusions received, and serum ferritin levels.

The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress.

Introduction: The immune-related lncRNAs (IRLs) are critical for the development of cervical cancer (CC), but it is still unclear how exactly ILRs contribute to CC. In this study, we aimed to examine the relationship between IRL and CC in detail. Methods: First, the RNAseq data and clinical data of CC patients were collected from The Cancer Genome Atlas (TCGA) database, along with the immune genes from the Import database. We used univariate cox and least absolute shrinkage and selection operator (lasso) to obtain IRLs for prediction after screening the variables. According to the expression levels and risk coefficients of IRLs, the riskscore were calculated. We analyzed the relationship between the model and oxidative stress. We stratified the risk model into two as the high and low-risk groups. We also evaluated the survival differences, immune cell differences, immunotherapeutic response differences, and drug sensitivity differences between the risk groups. Finally, the genes in the model were experimentally validated. Results: Based on the above analyses, we further selected four IRLs (TFAP2A.AS1, AP000911.1, AL133215.2, and LINC02078) to construct the risk model. The model was associated with oxidative-stress-related genes, especially SOD2 and OGG1. Patients in the high-risk group had a lower overall survival than those in the low-risk group. Riskscore was positively correlated with resting mast cells, neutrophils, and CD8+ T-cells. Patients in the low-risk group showed a greater sensitivity to immunosuppression therapy. In addition, we found that patients with the PIK3CA mutation were more sensitive to chemotherapeutic agents such as dasatinib, afatinib, dinaciclib and pelitinib. The function of AL133215.2 was verified, which was consistent with previous findings, and AL133215.2 exerted a pro-tumorigenic effect. We also found that AL133215.2 was closely associated with oxidative-stress-related pathways. Discussion: The results suggested that risk modeling might be useful for prognosticating patients with CC and opening up new routes for immunotherapy.

Corrigendum: An ultrasonic-based radiomics nomogram for distinguishing between benign and malignant solid renal masses.

[This corrects the article DOI: 10.3389/fonc.2022.847805.].

Post-transcriptional modification of m6A methylase METTL3 regulates ERK-induced androgen-deprived treatment resistance prostate cancer.

As the most common modification of RNA, N6-methyladenosin (m6A) has been confirmed to be involved in the occurrence and development of various cancers. However, the relationship between m6A and castration resistance prostate cancer (CRPC), has not been fully studied. By m6A-sequencing of patient cancer tissues, we identified that the overall level of m6A in CRPC was up-regulated than castration sensitive prostate cancer (CSPC). Based on the analysis of m6A-sequencing data, we found m6A modification level of HRas proto-oncogene, GTPase (HRAS) and mitogen-activated protein kinase kinase 2 (MEK2 or MAP2K2) were enhanced in CRPC. Specifically, tissue microarray analysis and molecular biology experiments confirmed that METTL3, an m6A "writer" up-regulated after castration, activated the ERK pathway to contribute to malignant phenotype including ADT resistance, cell proliferation and invasion. We revealed that METTL3-mediated ERK phosphorylation by stabilizing the transcription of HRAS and positively regulating the translation of MEK2. In the Enzalutamide-resistant (Enz-R) C4-2 and LNCap cell line (C4-2R, LNCapR) established in the current study, the ERK pathway was confirmed to be regulated by METTL3. We also found that applying antisense oligonucleotides (ASOs) to target the METTL3/ERK axis can restore Enzalutamide resistance in vitro and in vivo. In conclusion, METTL3 activated the ERK pathway and induced the resistance to Enzalutamide by regulating the m6A level of critical gene transcription in the ERK pathway.

mRNA Vaccine - A New Cancer Treatment Strategy.

The corresponding mRNA vaccines Comirnaty (BNT162b2) and Spikevax (mRNA-1273) have been authorized for emergency use since the COVID-19 outbreak. Most clinical researches have also discovered that the mRNA vaccine is a revolutionary strategy for preventing and treating numerous diseases, including cancers. Unlike viral vectors or DNA vaccines, mRNA vaccines cause the body to directly produce proteins following injection. Delivery vectors and mRNAs that encode tumor antigens or immunomodulatory molecules work together to trigger an anti-tumor response. Before mRNA vaccines may be employed in clinical trials, a number of challenges need to be resolved. These include establishing effective and safe delivery systems, generating successful mRNA vaccines against diverse types of cancers, and proposing improved combination therapy. Therefore, we need to improve vaccine-specific recognition and develop mRNA delivery mechanisms. This review summarizes the complete mRNA vaccines' elemental composition and discusses recent research progress and future direction for mRNA tumor vaccines.

Cellular Innate Biological Nano Confinements Control Cancer Metastasis Through Materials Seizing and Signaling Regulating.

Cancer is a debilitating disease, causing millions of deaths annually throughout the world. Due to their adaptive ability to meet nutritional demands, cancer cells often utilize more energy than normal cells. In order to develop new strategies to treat cancer, it is necessary to understand the underlying mechanisms of energy metabolism, which is yet largely unknown. Recent studies have shown that cellular innate nanodomains are involved in cellular energy metabolism and anabolism and GPCRs signaling regulation, which have a direct effect on cell fate and functions. Therefore, harnessing cellular innate nanodomains may evoke significant therapeutic impact and shift the research focus from exogenous nanomaterials to cellular innate nanodomains, which will have great potential to develop a new treatment modality for cancer. Keeping these points in view, we briefly discuss the impact of cellular innate nanodomains and their potential for advancing cancer therapeutics, and propose the concept of innate biological nano confinements, which include any innate structural and functional nano domains both in extracellular and intracellular with spatial heterogeneity.

Prevalence, General and Periodontal Risk Factors of Gastroesophageal Reflux Disease in China.

Purpose: There is insufficient information about the prevalence and risk factors of gastroesophageal reflux disease (GERD) in the Chinese adult population. We aimed to assess the prevalence and identify the risk factors of GERD in China. Methods: We collected data from a nationally representative sample (50,991 subjects) of Chinese adults from a large nation-wide cross-sectional survey. GERD was diagnosed by a standardized Chinese-language GERD questionnaire with a score of ≥ 8. The demographic characteristics, comorbidities and periodontal factors of all participants were collected. Results: Fifty-thousands-one-hundred-eighty-three participants were finally included in this study. The overall prevalence of GERD was 5.6% (95% CI, 5.4-5.8%) among the general Chinese population aged 20 years or older. Women, smokers, and people with older age, BMI ≥ 25.0 kg/m2, urban residence, lower education level or comorbidities were more prevalent with GERD (p < 0.001). Symptoms of severe periodontitis (OR = 1.40, 95% CI 1.28-1.52, p < 0.001) and lower frequency of tooth brushing (OR = 2.01, 95% CI 1.76-2.29, p < 0.001) were significantly associated with risk of GERD. Conclusion: Symptom-based GERD is highly prevalent in the Chinese population. Overweight and smoking are major preventable risk factors for GERD. Periodontal factors are novel potential risk factors for GERD and should be given more attention in GERD prevention.

Group 1 and 3 innate lymphoid cells are increased in oral lichen planus and oral lichenoid lesions.

OBJECTIVES: Innate lymphoid cells (ILCs) are vital innate immune cells cooperating with T cells. While their phenotypes and functions in oral mucosa kept unclear yet. In the present study, the relative proportions and distribution of different ILC subsets in oral mucosa of oral lichen planus (OLP), oral lichenoid lesions (OLL), and controls were compared. SUBJECTS AND METHODS: Oral mucosal samples were collected from control (n = 29), OLP (n = 20), and OLL (n = 22) donors. ILCs subsets were characterized in single-cell suspensions by flow cytometry. Immunohistochemistry was performed to locate the CD127+ cells in situ. RESULTS: ILCs were present in healthy and increased infiltration in OLP/OLL (p = 0.0092, p = 0.0216). Infiltration of ILC1 increased in OLP/OLL mucosa (p = 0.0225, p = 0.0399), as did the infiltration of ILC3 increase in OLL mucosa (p = 0.0128). The ILC2/ILCs ratio was significantly reduced in OLP and OLL (p = 0.0124, p = 0.0346). CD127+ cells were mainly located closely at the basement membrane. CONCLUSIONS: The results of increased ILC1, decreased ILC2, and increased ILC3 suggested that changes of ILC distributions in oral mucosa may be relevant to persistent inflammation in local tissues, by promoting immune factors and weakening repair capacity.

A deep learning-based diagnostic pattern for ultrasound breast imaging: can it reduce unnecessary biopsy?

Background: Early studies have demonstrated the potential of deep learning in bringing revolutionary changes in medical analysis. However, it is unknown which deep learning based diagnostic pattern is more effective for differentiating malignant and benign breast lesions (BLs) and can assist radiologists to reduce unnecessary biopsies. Methods: A total of 506 malignant BLs and 557 benign BLs were enrolled in this study after excluding incomplete ultrasound images. 396 malignant BLs and 447 benign BLs were included in the training cohort while 110 malignant and 110 benign BLs were included in the validation cohort. All BLs in the training and validation cohort were biopsy-proven. The most common convolutional neural networks (VGG-16 and VGG-19) were applied to identify malignant and benign BLs using grey-scale ultrasound images. Two radiologists determined the malignant (suggestion for biopsy) and benign (suggestion for follow-up) BLs with a 2-step reading session. The first step was based on conventional ultrasound (US) images alone to make a biopsy or follow-up decision. The second step was to take deep learning results into account for the decision adjustment. If a deep learning result of a first-classified benign BL was above the cut-off value, then it was re-classified as malignant. Results: In terms of area under the curve (AUC), the VGG-19 model yielded the best diagnostic performance in both training [0.939, 95% confidence interval (CI): 0.924-0.954] and testing dataset (0.959, 95% CI: 0.937-0.982). With the aid of deep learning models, the AUC of radiologists improved from 0.805 (95% CI: 0.744-0.865) to 0.827 (95% CI: 0.771-0.875, VGG-16) and 0.914 (95% CI: 0.871-0.957, VGG-19). The unnecessary biopsies decreased from 10.0% (11/110) to 8.2% (9/110) (assisted by VGG-16) and 0.9% (1/110) (assisted by VGG-19). Conclusions: The application of deep learning patterns in breast US may improve the diagnostic performance of radiologists by offering a second opinion. And thus, the assist of deep learning algorithm can considerably reduce the unnecessary biopsy rate in the clinical management of breast lesions.

Exploration of Clove Bud (Syzygium aromaticum) Essential Oil as a Novel Attractant against Bactrocera dorsalis (Hendel) and Its Safety Evaluation.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive polyphagous species that targets many economically important fruits and vegetables. The primary control of B. dorsalis relies mainly on the use of synthetic chemicals, and excessive use of these chemicals has adverse effects on both the environment and human health. Environmentally friendly management of pests involving plant essential oils is useful for controlling the populations of pests responsible for decreasing the yields and quality of crops. In the present study, we demonstrate that clove bud essential oil (CBEO) is strongly attractive to sexually mature males. Mature males responded to the CBEO differently throughout the day; the strongest response was elicited during the day and decreased at dusk. Virgin and mated mature males did not respond differently to CBEO. No obvious response behaviour to the CBEO was observed in two species of beneficial natural predator ladybirds. In addition, a cytotoxicity assessment demonstrated that CBEO is nontoxic to normal human and mouse cells. Based on our laboratory experiments, CBEO may serve as a promising, sustainable, and environmentally friendly attractant for B. dorsalis males; however, field experiments are needed to confirm this hypothesis.

Marine collagen peptides: A novel biomaterial for the healing of oral mucosal ulcers.

The purpose of this study was to analyze the therapeutic effects of marine collagen peptides (MCPs) from tilapia skin on oral mucosal ulcers in a rat model. CCK-8 and wound healing assays were performed in vitro to evaluate proliferation and migration of L929 cells after treatment with MCPs. The effects of MCPs on the healing of oral mucosal ulcers in a rat model were macroscopically and microscopically analyzed in vivo. Results showed that MCPs promoted proliferation and migration of L929 cells. Moreover, 75%MCPs enhanced the ulcer healing process, suppressed inflammatory response and up-regulated the expression levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). MCPs are potentially used as a new therapeutic strategy for oral mucosal ulceration.

Postsurgical Pain and Implant Osseointegration Failure: A Case Control Study.

Aim: The relationship between postsurgical pain and osseointegration was evaluated and analyzed in this study. Material and method. 27 patients, ranging in age from 35 to 72 years old, 12 males and 15 females, who received dental implants and failed to achieve osseointegration from Tianjin Medical University Second Hospital, were analyzed and studied in the following aspects: bone density, initial torque, one- or two-stage surgery, postsurgical pain, postsurgical swelling, and radiographic evidence of osseointegration failure. Result: 5 patients were assessed to be D4 bone density and 7 cases were assessed to be D3 bone density, 2 patients were assessed to be D2 bone density and 13 patients were assessed to be D1 bone density. All cases were documented with clinically acceptable initial torque. Among the 27 cases, 2 of them were one-stage nonsubmerged surgery and 25 cases were two-stage submerged surgery. 25 out of 27 patients reported moderate to severe pain lasting for more than 72 hours. Radiologic examinations failed to offer any indication of poor osseointegration in the 7-day postsurgical follow-up. Conclusion: Moderate to severe postsurgical pain lasting more than 72 hours displays high odd ratio of poor osseointegrate. The radiological examinations alone failed to offer any valuable evidence for the early detection of osseointegration failure in this study.