Aspirin and Celecoxib Regulate Notch1/Hes1 Pathway to Prevent Pressure Overload-Induced Myocardial Hypertrophy.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1ß) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.

Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer.

BACKGROUND: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery. METHODS: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study. RESULTS: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful. CONCLUSION: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

The machine learning-based model for lateral lymph node metastasis of thyroid medullary carcinoma improved the prediction ability of occult metastasis.

BACKGROUND: For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed. METHODS: From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN0-1a patients. RESULTS: A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN0-1a patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64). CONCLUSIONS: We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN0-1a patients more accurately, then benefit the decision of prophylactic LND.

Comprehensive investigation into the influence of glycosylation on head and neck squamous cell carcinoma and development of a prognostic model for risk assessment and anticipating immunotherapy.

Background: It has been well established that glycosylation plays a pivotal role in initiation, progression, and therapy resistance of several cancers. However, the correlations between glycosylation and head and neck squamous cell carcinoma (HNSCC) have not been elucidated in detail. Methods: The paramount genes governing glycosylation were discerned via the utilization of the Protein-Protein Interaction (PPI) network and correlation analysis, coupled with single-cell RNA sequencing (scRNA-seq) analysis. To construct risk models exhibiting heightened predictive efficacy, cox- and lasso-regression methodologies were employed, and the veracity of these models was substantiated across both internal and external datasets. Subsequently, an exploration into the distinctions within the tumor microenvironment (TME), immunotherapy responses, and enriched pathways among disparate risk cohorts ensued. Ultimately, cell experiments were conducted to validate the consequential impact of SMS in Head and Neck Squamous Cell Carcinoma (HNSCC). Results: A total of 184 genes orchestrating glycosylation were delineated for subsequent scrutiny. Employing cox- and lasso-regression methodologies, we fashioned a 3-gene signature, proficient in prognosticating the outcomes for patients afflicted with HNSCC. Noteworthy observations encompassed distinctions in the Tumor Microenvironment (TME), levels of immune cell infiltration, and the presence of immune checkpoint markers among divergent risk cohorts, holding potentially consequential implications for the clinical management of HNSCC patients. Conclusion: The prognosis of HNSCC can be proficiently anticipated through risk signatures based on Glycosylation-related genes (GRGs). A thorough delineation of the GRGs signature in HNSCC holds the potential to facilitate the interpretation of HNSCC's responsiveness to immunotherapy and provide innovative strategies for cancer treatment.

Ganoderma spore lipid ameliorates docetaxel, cisplatin, and 5-fluorouracil chemotherapy-induced damage to bone marrow mesenchymal stem cells and hematopoiesis.

BACKGROUND: A triplet chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TPF) is used to treat head and neck squamous cell carcinoma; however, it is toxic to bone marrow mesenchymal stem cells (BMSCs). We previously demonstrated that Ganoderma spore lipid (GSL) protect BMSCs against cyclophosphamide toxicity. In this study, we investigated the protective effects of GSL against TPF-induced BMSCs and hematopoietic damage. METHODS: BMSCs and C57BL/6 mice were divided into control, TPF, co-treatment (simultaneously treated with GSL and TPF for 2 days), and pre-treatment (treated with GSL for 7 days before 2 days of TPF treatment) groups. In vitro, morphology, phenotype, proliferation, senescence, apoptosis, reactive oxygen species (ROS), and differentiation of BMSCs were evaluated. In vivo, peripheral platelets (PLTs) and white blood cells (WBCs) from mouse venous blood were quantified. Bone marrow cells were isolated for hematopoietic colony-forming examination. RESULTS: In vitro, GSL significantly alleviated TPF-induced damage to BMSCs compared with the TPF group, recovering their morphology, phenotype, proliferation, and differentiation capacity (p < 0.05). Annexin V/PI and senescence-associated ß-galactosidase staining showed that GSL inhibited apoptosis and delayed senescence in TPF-treated BMSCs (p < 0.05). GSL downregulated the expression of caspase-3 and reduced ROS formation (p < 0.05). In vivo, GSL restored the number of peripheral PLTs and WBCs and protected the colony-forming capacity of bone marrow cells (p < 0.05). CONCLUSIONS: GSL efficiently protected BMSCs from damage caused by TPF and recovered hematopoiesis.

Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC. METHODS: We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student's t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong's test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models. RESULTS: The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM. CONCLUSIONS: We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.

Study on the related factors of TCM constitution and hemodynamics in patients with coronary heart disease.

Background: The concepts of "individualization" and "preventive treatment" should be incorporated into the precise diagnosis and treatment of coronary heart disease (CHD). Both hemodynamics and Chinese medicine constitution studies align with these two concepts. Methods: This study utilized data from 81 patients with CHD, including 12 patients with balanced constitution (BC), 20 patients with blood stasis constitution (BSC), 17 patients with phlegm-dampness constitution (PDC), 15 patients with qi-deficiency constitution (QDC), and 17 patients with other constitutions. Clinical data provided information on the patients' blood property, heart function, degree of coronary stenosis, coronary hemodynamics, and so on. These parameters were compared between patients with balanced constitution vs. biased constitutions as well as between those with blood stasis constitution, phlegm-dampness constitution, and qi-deficiency constitution. Results: Compared to biased constitution (BC), patients with balanced constitution exhibited lower total cholesterol (TC) levels and low-density lipoprotein (LDL) levels. Additionally, they had lighter stenosis degrees in the Left anterior descending branch (LAD) and Left circumflex branch (LCX) branches. The hemodynamic condition of the LAD and LCX was better for those with balanced constitution; however there was no difference in heart function. Among the groups categorized by blood stasis, phlegm dampness or qi deficiency constituions, patients classified under phlegm dampness had higher levels of LDL compared to those classified under blood stasis or qi deficiency, while patients classified under qi deficiency had higher levels of blood glucose compared to those classified under blood stasis or phlegm dampness. Hemodynamic environments also differed among the LAD and LCX for each group but there were no significant differences observed in heart function or degree of coronary stenosis among these three groups. Conclusion: The balanced constitution demonstrates superior blood property, degree of coronary artery stenosis, and coronary hemodynamics compared to the biased constitution. Furthermore, among the three constitutions with CHD, variations in blood property and certain hemodynamic parameters are observed. These findings emphasize the significant clinical value of incorporating physical factors into the diagnosis and treatment of patients with CHD.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma.

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma (HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells' expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancer-associated fibroblasts (CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-to-mesenchymal transition (EMT) model and the mechanism of drug resistance, as well as its clinical value.

An Adaptive Parameterized Domain Mapping Method and Its Application in Wheel-Rail Coupled Fault Diagnosis for Rail Vehicles.

The rapid development of cities in recent years has increased the operational pressure of rail vehicles, and due to the characteristics of rail vehicles, including harsh operating environment, frequent starting and braking, resulting in rails and wheels being prone to rail corrugation, polygons, flat scars and other faults. These faults are coupled in actual operation, leading to the deterioration of the wheel-rail contact relationship and causing harm to driving safety. Hence, the accurate detection of wheel-rail coupled faults will improve the safety of rail vehicles' operation. The dynamic modeling of rail vehicles is carried out to establish the character models of wheel-rail faults including rail corrugation, polygonization and flat scars to explore the coupling relationship and characteristics under variable speed conditions and to obtain the vertical acceleration of the axle box. An APDM time-frequency analysis method is proposed in this paper based on the PDMF adopting Rényi entropy as the evaluation index and employing a WOA to optimize the parameter set. The number of iterations of the WOA adopted in this paper is decreased by 26% and 23%, respectively, compared with PSO and SSA, which means that the WOA performs at faster convergence speed and with a more accurate Rényi entropy value. Additionally, TFR obtained using APDM realizes the localization and extraction of the coupled fault characteristics under rail vehicles' variable speed working conditions with higher energy concentration and stronger noise resistance corresponding to prominent ability of fault diagnosis. Finally, the effectiveness of the proposed method is verified using simulation and experimental results that prove the engineering application value of the proposed method.

Identification of Putative Bacterial Pathogens for Orofacial Granulomatosis Based on 16S rRNA Metagenomic Analysis.

Orofacial granulomatosis (OFG) is a chronic inflammatory disease characterized by nontender swelling of the orofacial tissues, the underlying cause of which remains unknown. Our previous study demonstrated that tooth apical periodontitis (AP) is involved in the development of OFG. To characterize the AP bacterial signatures of OFG patients and identify possible pathogenic bacteria that cause OFG, the compositions of the AP microbiotas in OFG patients and controls were compared using 16S rRNA gene sequencing. Pure cultures of putative bacterial pathogens were established by growing bacteria as colonies followed by purification, identification, and enrichment and then were injected into animal models to determine the causative bacteria contributing to OFG. A specific AP microbiota signature in the OFG patients was shown, characterized by the predominance of phyla Firmicutes and Proteobacteria, notably members of the genera Streptococcus, Lactobacillus, and Neisseria, were found. Streptococcus spp., Lactobacillus casei, Neisseria subflava, Veillonella parvula, and Actinomyces spp. from OFG patients were isolated and successfully cultured in vitro and then injected into mice. Ultimately, footpad injection with N. subflava elicited granulomatous inflammation. IMPORTANCE Infectious agents have long been considered to play a role in the initiation of OFG; however, a direct causal relationship between microbes and OFG has not yet been established. In this study, a unique AP microbiota signature was identified in OFG patients. Moreover, we successfully isolated candidate bacteria from AP lesions of OFG patients and assessed their pathogenicity in laboratory mice. Findings from this study may help provide in-depth insights into the role of microbes in OFG development, providing the basis for targeted therapeutic approaches for OFG.

Autophagy regulates anti-angiogenic property of lenvatinib in thyroid cancer.

We aimed to explore the role of lenvatinib-mediated autophagy in papillary thyroid cancer (PTC). K1 and BCPAP, were tested for cell viability, proliferation, and apoptosis after treatment with lenvatinib or chloroquine (CQ) or both. The levels of angiogenesis vascular endothelial growth factor A (VEGFA) were measured by ELISA. Transwell and wound-healing assays were performed using endothelial HUVECs cells. The dynamics of microvessels were detected by tubular formation assay. Western blotting was used to determine the expression of LC3-I/II and Atg-7 and alterations in the PI3K/Akt/mTOR and MEK/ERK pathways. In vivo tumor growth assay and immunohistochemical staining (IHC) was also performed. The results showed that lenvatinib inhibited the viability of K1 and BCPAP cells and caused apoptosis. We further showed that lenvatinib also upregulated autophagy levels in thyroid cancer cells in a dose-dependent manner through the PI3K/Akt/mTOR and MEK/ERK pathways. Co-administration of lenvatinib with CQ resulted in a greater decrease of VEGFA in the tumor supernatant than with either lenvatinib or CQ alone. Autophagy inhibition enhanced the cytotoxicity and anti-angiogenic ability of lenvatinib, which was supported by the HUVECs migration, wound healing, and tube formation assays. Inhibiting autophagy chemically or genetically enhanced lenvatinib's cytotoxic effects and anti-angiogenic efficacy in thyroid cancer cells in vitro and in vivo. In conclusion, lenvatinib inhibited cell viability and induced apoptosis and autophagy in human PTC cells. Significantly, the combination of lenvatinib and autophagy inhibition may represent a novel and effective treatment option for PTC, which may be able to overcome drug resistance.

Intramolecular trapping of spiro radicals to produce unusual cyclization products from usual migration substrates.

A conceptually new methodology to give unusual cyclization products from usual migration substrates was disclosed. The highly complex and structurally important and valuable spirocyclic compounds were produced through radical addition, intramolecular cyclization and ring opening instead of usual migration to the di-functionalization products of olefins. Furthermore, a plausible mechanism was proposed based on a series of mechanistic studies including radical trapping, radical clock, verification experiments of intermediates, isotope labeling and KIE experiments.

The critical role of IFNγ in the epidermotropic migration of lymphocytes in oral lichen planus.

INTRODUCTION: The chemokines play a crucial role in the recruitment of lymphocytes in oral lichen planus, and the activated epithelial cells are the main producers of the chemokines. However, the signals provoking chemokine secretion still remain to be elucidated. METHODS: The global expression profile of chemokines in oral epithelial cell line induced by IFNγ was determined by microarray analysis. The gene and protein expression was validated in primary culture of oral epithelial cells, and the effects of IFNγ on regulating chemokine production were compared with that of TNFα and IL2. Moreover, the capability of primary culture of oral epithelial cells to attract peripheral lymphocytes in response to IFNγ was investigated in oral lichen planus patients, and the cell phenotype of the recruited lymphocytes was analyzed using flow cytometry. RESULTS: IFNγ triggered the expression of multiple chemokines in the oral epithelial cells. The expression pattern of the chemokines closely resembled that in the epithelial cell layer of oral lichen planus lesions. Compared with IL2 and TNFα, IFNγ demonstrated a distinct maximal effect on the chemokines secretion in primary culture of oral epithelial cells. The migration of peripheral lymphocytes toward the culture supernatant of IFNγ-treated primary culture of oral epithelial cells was significantly enhanced in the oral lichen planus group compared to that in the healthy control group. CONCLUSION: IFNγ plays an important role in the chemokine secretion and epidermotropic migration of lymphocytes in oral lichen planus.

Mechanism of Astrin in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma(HNSCC) is a malignant epidermal tumor that seriously threatens human life and health. The main factors affecting the death of patients are local recurrence and lymph node metastasis. Astrin antibody is the basic component of the mitotic spindle required for normal chromosome separation and later development. There are few domestic studies on the mechanism of Astrin in HNSCC. Based on this, this article is studying Astrin in HNSCC. The expression and function of Astrin, and analyze its correlation with clinical pathological parameters and prognosis of patients, and further explore the relevant mechanisms involved in the progression of Astrin in HNSCC. In this experiment, the real-time fluorescent quantitative polymerase chain reaction (PCR) method was used to detect the expression of the Astrin antibody in HNSCC cell lines A and B. Secondly, this article will focus on high metastatic HNSCC cells B. Divided into five groups (blank control group, overexpression positive group, overexpression negative control group, expression suppression positive group, expression suppression negative control group), using real-time fluorescent quantitative PCR technology to detect the expression of Astrin in each group, and then speculate the mechanism of Astrin in HNSCC. Experiments have shown that Astrin is expressed in A and B cells, but its expression in B is significantly higher than its expression in A, and the difference is statistically significant (P<0.001). This shows that the inhibition of Astrin expression has a significant anti-tumor effect and that Astrin plays an important role in the occurrence and development of tumors. It is expected to provide new ideas and reference basis for exploring new therapeutic strategies for targeted therapy of HNSCC.

Analysis of clinical presentations, lip transepidermal water loss and associated dermatological conditions in patients with chronic cheilitis.

Chronic cheilitis (CC) is a spectrum of inflammatory changes of unknown etiology that affect the vermilion of the lips. This study aimed to describe the epidemiology, clinical presentations and risk factors of CC. Patients with CC were recruited from the National Clinical Research Center for Oral Disease of China. A convenience sample of inhabitants who live in the same geographical region were recruited as the control group. The lip skin transepidermal water loss (TEWL) and capacitance of CC patients were compared with that of age- and gender-matched controls. Our results demonstrated that of the 109 patients with CC, 72 (66.1%; 95% CI: 57.0-75.1%) were female. The common clinical presentations of CC consisted of desquamation (n = 99; 90.8%), and/or chapping (n = 81; 74.3%), and/or pruritus (n = 64; 58.7%). Multivariable analysis showed that allergic dermatologic diseases (P < 0.001; OR: 4.5; 95% CI: 2.4-8.4), anemia (P = 0.001; OR: 3.3; 95% CI: 1.5-7.5), and indoor/outdoor alternate working environment (P < 0.001; OR: 2.1; 95% CI: 1.5-2.8) were the significant risk factors for CC. The mean lip skin TEWL was found to be significantly higher, while the capacitance was lower in CC patients compared to that of control individuals. This study provides insights into the etiopathogenesis of CC and may help clinicians to identify the most effective management strategies.

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer.

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERß), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERß genes undergo the alternative RNA splicing, some ERα and ERß isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERß have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERß isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERß against thyroid cancer.

A Novel Method to Determine the Cause of Left Internal Mammary Artery Instant Non-Patency Based on Transit Time Flow Measurement.

Objective: After coronary artery bypass grafting (CABG) surgery, the main causes of poor instant patency of left internal mammary arteries (LIMAs) are competitive flow and anastomotic stenosis, but how to determine the cause of LIMA non-patency without interfering with the native coronary artery is still a difficult problem to be solved urgently. Methods: In this study, a 0D-3D coupled multiscaled CABG model of anastomotic stenosis and competitive flow was constructed. After calculation, the flow waveform of the LIMA was extracted, and the waveform shape, common clinical parameters (average flow, PI, and DF), and graft flow FFT ratio results (F0/H1 and F0/H2) were analyzed. Results: For LIMA, these three common clinical parameters did not differ significantly between the anastomotic stenosis group and competitive flow group. However, the waveform shape and FFT ratio (especially F0/H2) of the competitive flow group were significantly different from those of the anastomotic stenosis group. When the cause was competitive flow, there was systolic backflow, and F0/H2 was too high (>14.89). When the cause was anastomotic stenosis, the waveform maintained a bimodal state and F0/H2 was in a normal state (about 1.17). Conclusion: When poor instant patency of the LIMA is found after CABG, the causes can be determined by graft flow waveform shape and F0/H2.

Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer.

By multiple transcriptome datasets (TCGA, GSE59102, GSE25727, GSE27020 and GSE65858) and multi-omics (RNA-seq, SNP, CNV, DNA methylation) in-depth analysis, we found that cancer germline antigen (CGA) family/genes MAGEB2 is involved in the imitation, progression and prognosis in LC as well as correlated positively with lymphatic metastasis and negatively with DNA methylation. Then, in vitro experiment verified that MAGEB2 expression renders significant alteration in LC tissues and cells via immunohistochemical (IHC), qRT-PCR and western blot (WB), and up-regulation of MAGEB2 expression could facilitate the proliferation, migration and invasion of LC cells and vice versa. Subsequently, MAGEB2 knockdown suppressed tumor growth and lung metastasis in vivo animal experiment, while MAGEB2 overexpression promoted tumor growth and lung metastasis. Lastly, MAGEB2 is significantly associated with immune cell infiltration (CD8+ T cells particularly, IHC staining confirmed that as the protein expression of MAGEB2 increased, the protein level of CD8 (representing tumor-infiltrating CD8 + T cells) decreased in vitro), immunomodulators (knockdown or overexpression of MAGEB2 on LC cell lines can significantly affect the chemokine/cytokine secretion in vitro), and immunogenicity(TMB) in LC, which hints that MAGEB2 is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for LC patients.

Necessity of Intraoperative Level IIA Lymph Node Dissection in Patients with Carotid Body Tumors: A Retrospective Study of 126 Cases.

BACKGROUND: Carotid body tumors (CBTs) are relatively uncommon neoplasms that rarely have malignant potential. However, malignant CBTs (MCBTs) are still associated with a poor prognosis and the treatment is still challenging clinically. Therefore, we evaluated the necessity of intraoperative level IIA lymph node dissection in patients with CBT. METHODS: The clinical characteristics, intraoperative details, and pathological diagnosis of 126 CBT patients who had undergone surgery were retrospectively reviewed. The patients were divided into 2 groups according to whether level IIA lymph node dissection was performed. The prognosis was analyzed using Kaplan-Meier curves and Cox model multivariate survival analysis. RESULTS: Among the 126 patients, 7 patients (10.3%) in the selective lymph node dissection (SLND) group (68 patients) were diagnosed with MCBTs with evidence of lymph node metastasis. Two patients (3.4%) in the lymph node nondissection (LNND) group (58 patients) were diagnosed with MCBTs later after the second operation because they could not be diagnosed as malignant initially because of the lack of lymph node pathology results although the pathology of the primary lesion showed features of malignancy. The SLND group had a significantly higher relapse-free survival rate than the LNND group (94.1% vs. 79.3%, p = 0.021). Patients with a confirmed diagnosis had a better prognosis than those with insufficient evidence of a malignancy due to the lack of lymph node information. Twenty-nine patients in the SLND group and 26 patients in the LNND group had postoperative nerve injuries, with no significant difference between the groups (p = 0.879). CONCLUSION: Intraoperative dissection of level IIA lymph nodes around the tumor in CBT patients can help improve the diagnosis and prognosis of MCBTs without causing additional cranial nerve injury.