Learning curve of trans-areola single-site endoscopic thyroidectomy in a high-volume center: A CUSUM-based assessment.

BACKGROUND: Limited attempts have been made in trans-areola single-site endoscopic thyroidectomy (TASSET) due to technical challenges and the lengthy time for proficiency. This study aimed to define the learning curve of TASSET and to describe improvements in operative performance over time. METHODS: Based on 222 consecutive TASSET procedures, the learning curve was established according to the operation time by using cumulative sum analysis (CUSUM). The end-point of learning curve was defined as the number of cases necessitated to reach the initial surgical proficiency stage. The demographic information, surgical and oncological outcomes, surgical stress, and postoperative complications were also analyzed. RESULTS: There were 70 cases of simple lobectomy for benign nodules and 152 cases of lobectomy with central neck dissection (CND) for malignancy. The mean operative time was 106.54 ± 38.07 min (range: 46-274 min). The learning curve identified two phases: the skill acquisition phase (Case 1-Case 41) and the proficiency phase (Case 42-Case 222). There were no significant differences in demographic information, drainage amount and duration, oncological outcomes, and postoperative complications between the two phases (p > 0.05). Both operation time and postoperative hospitalization decreased significantly in Phase 2 (154.63 ± 52.21 vs. 95.64 ± 22.96 min, p < 0.001; 4.12 ± 0.93 vs. 3.65 ± 0.63 days, p < 0.001). Additionally, the mean variations of surgical stress factors (C-reactive protein and erythrocyte sedimentation rate) decreased significantly as the phase progress. The case number required for proficiency phase in benign and malignant tumor were 18 and 33, respectively, and lymph node resection posed a significant impact on the endpoint of the learning curve (p < 0.001). Meanwhile, the size of nodule showed no significant impact (p = 0.622). For right-handed surgeons, 16 cases and 25 cases were required for technical competence in left-sided and right-sided lesions, respectively, and no significant difference reached (p = 0.266). CONCLUSIONS: TASSET has demonstrated safe and technically feasible with comparable oncological outcomes. Experience of 41 cases was required for surgical competence and proficiency. The initial learning stage could be more quickly adopted by high-volume thyroid surgeons with standardized procedures.

Automated diagnosis and management of follicular thyroid nodules based on the devised small-dataset interpretable foreground optimization network deep learning: a multicenter diagnostic study.

BACKGROUND: Currently, follicular thyroid carcinoma (FTC) has a relatively low incidence with a lack of effective preoperative diagnostic means. To reduce the need for invasive diagnostic procedures and to address information deficiencies inherent in a small dataset, we utilized interpretable foreground optimization network deep learning to develop a reliable preoperative FTC detection system. METHODS: In this study, a deep learning model (FThyNet) was established using preoperative ultrasound images. Data on patients in the training and internal validation cohort ( n =432) were obtained from Ruijin Hospital, China. Data on patients in the external validation cohort ( n =71) were obtained from four other clinical centers. We evaluated the predictive performance of FThyNet and its ability to generalize across multiple external centers and compared the results yielded with assessments from physicians directly predicting FTC outcomes. In addition, the influence of texture information around the nodule edge on the prediction results was evaluated. RESULTS: FThyNet had a consistently high accuracy in predicting FTC with an area under the receiver operating characteristic curve (AUC) of 89.0% [95% CI 87.0-90.9]. Particularly, the AUC for grossly invasive FTC reached 90.3%, which was significantly higher than that of the radiologists (56.1% [95% CI 51.8-60.3]). The parametric visualization study found that those nodules with blurred edges and relatively distorted surrounding textures were more likely to have FTC. Furthermore, edge texture information played an important role in FTC prediction with an AUC of 68.3% [95% CI 61.5-75.5], and highly invasive malignancies had the highest texture complexity. CONCLUSION: FThyNet could effectively predict FTC, provide explanations consistent with pathological knowledge, and improve clinical understanding of the disease.

The proposed modification of TNM staging and therapeutic strategy for skip metastasis in papillary thyroid carcinoma: A multicenter retrospective cohort study.

BACKGROUND: Skip metastasis is a special type of lateral lymph node metastasis, which is not classified definitely by the eighth edition of the AJCC TNM staging system. The aim of the research was to study the prognosis of skip metastasis in PTC patients, and carry out a more appropriate N staging for skip metastasis. METHODS: Study subjects were 3167 patients with papillary thyroid carcinoma (PTC), who underwent thyroidectomy at three clinical centers from 2016 to 2019. We identified two well-balanced cohorts matched on the basis of propensity score. RESULTS: During a median follow-up of 42 months, recurrence occurred in 68 (4.3%) patients with lymph node metastasis. 34 cases recurred in 1120 patients with central lymph node metastasis (N1a), and 34 recurred in 461 patients with lateral lymph node metastasis (N1b), among which 73 patients were diagnosis with skip metastasis. The RFS of N1a was significantly lower than that of N1b (p < 0.001). After propensity-score matching, recurrence rate was significantly lower in the skip metastasis group than in the LLNM group (p = 0.039), whereas the rate was similar in the skip metastasis groups and the CLNM group (p = 0.29). CONCLUSIONS: In conclusion, our study indicated that, among patients with LLNM, those with positive skip metastasis showed significantly lower recurrence, exhibiting a similar rucurrence tendency as patients with CLNM. Thus, skip metastasis could be categorized into N1a stage rather than N1b stage based on the AJCC TNM staging system. The downstaging of skip metastasis may reveal more conservative treatment strategy.

Central and lateral neck involvement in papillary thyroid carcinoma patients with or without thyroid capsular invasion: A multi-center analysis.

Purposes: To quantitatively predict the probability of cervical lymph node metastasis for papillary thyroid carcinomas (PTC) patients with or without thyroid capsular invasion (TCI), to guide the decision-making of management strategies for neck regions. Methods: A total of 998 PTC patients from three medical centers were retrospectively analyzed. Results: Patients with positive TCI (TCI group) exhibited higher risks for both CLNM and LLNM than those with negative TCI (no-TCI group). Patients receiving lateral lymph node dissection showed significantly higher incidence of relatively severe postoperative complications. For no-TCI group, factors including age less than 55 years old, male, the presence of bilateral disease and multifocality, and maximum tumor diameter (MTD)>=0.5cm were confirmed to be independent risk factors for CLNM, while the presence of bilateral disease and ipsilateral nodular goiter (iNG), and maximum positive CLN diameter (MCLND)>1.0cm independent factors for LLNM. Independent risk factors of LLNM for patients within the TCI group included MCLND>1.0cm, positive CLN number>=3, and the presence of iNG. Predictive models of CLNM and LLNM were established based on the aforementioned risk factors for patients within no-TCI and TCI groups. A meticulous and comprehensive risk stratification flow chart was established for a more accurate evaluation of central neck involvement including both CLNM and LLNM risk in PTC patients. Conclusions: A meticulous and comprehensive stratification flow chart for PTC patients for quantitatively evaluating both CLNM and LLNM was constructed.

Return to Work and Mortality in Breast Cancer Survivors: A 11-Year Longitudinal Study.

Breast cancer is the most commonly occurring cancer in women, and it is a major cause of cancer death around the world. With the development of diagnostic methods and improvements in treatment methods, the incidence rate of breast cancer and the number of breast cancer survivors continue to simultaneously increase. We used national registry database to analyze the features that affect employment and return to work among breast cancer survivors. A total of 23,220 employees, who were newly diagnosed with breast cancer were recruited based on the Labor Insurance Database (LID), the Taiwan Cancer Registry (TCR), and National Health Insurance Research Database (NHIRD) during the period 2004-2015. The correlations between return to work (RTW) and independent confounding factors were examined using Cox proportional hazards model. Survival probability was analyzed using the Kaplan-Meir method. After adjusting for confounding variables, cancer stage, chemotherapy and higher income were significantly negatively correlated with RTW. Among breast cancer survivors, RTW was found to be related to a lower risk of all-cause mortality in both the unadjusted and fully adjusted model. Patients who had RTW exhibited better survival in all stages. Work-, disease- and treatment-related factors influenced RTW among employees with breast cancer. RTW was associated with better breast cancer survival. Our study demonstrates the impact of RTW and the associated factors on breast cancer survivorship.

Copper metabolism patterns and tumor microenvironment characterization in colon adenocarcinoma.

Copper participates in biological processes such as oxygen metabolism and iron uptake, and is a key factor in immune regulation. Based on the transcription data, mutation data and clinical data of colon adenocarcinoma (COAD) patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Profiling Interactive Analysis (GEPIA2) database, the expression and mutation of copper metabolization-related genes in COAD patients and their correlation with tumor immune microenvironment were analyzed. Copper metabolization-related genes (CMRGs) were used to construct COAD subtypes and prognostic risk models for COAD patients. Furthermore, Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curve were used to analyze the clinical value of COAD subtypes and genotyping models in distinguishing clinical characteristics of patients, and the immune infiltration of patients with different genotypes was analyzed. Finally, the clinical tissue samples from COAD patients were used to analyze the mRNA expression of genes in risk model between tumor and normal tissues by the method of Polymerase Chain Reaction (PCR). Of the 479 CMRGs, 68 genes were differentially expressed in normal and tumor tissues of COAD patients in TCGA and GEPIA2. Two subtypes with different clinical and immunological characteristics were identified by using 482 genes related to copper metabolism. Finally, a prognostic risk model consisting of five CMRGs was constructed, which could not only predict the prognosis of patients, but also correlated with COAD subtypes. In addition, some genes (glutathione S-transferase mu 1, cyclin D1and cytochrome P450 family 2 subfamily S member 1) in risk model was show significant difference between normal and tumor tissues. The COAD subtypes identified by CMRGs can help clinically distinguish patients with different prognosis and tumor progression, and the risk score can assist in clinical evaluation of patient prognosis, serving as a valuable biomarker for COAD immunotherapy.

Effect of FOXP2 transcription factor on immune infiltration of thyroid cancer and its potential clinical value.

Background: The clinical outcomes are not always favorable in certain thyroid cancer patients. The effect of Forkhead-box family on immune cells infiltration and tumor microenvironment in thyroid cancer was explored. The role of FOXP2 in tumor invasion and recurrence was investigated consequently. Methods: TIMER and GEPIA were firstly employed to compare FOXPs expression in normal and cancer tissues from multiple human cancers. The results from database were confirmed by quantitative Real Time-PCR and Western blot in matched thyroid cancer and adjacent normal tissues, in addition to a panel of thyroid cancer cell lines and normal thyroid cell. GEPIA platform was employed to discover the possibility of FOXPs as prognostic indicator. TISIBD and UACLCAN were then employed to estimate the influence of FOXPs on lymph node metastasis and tumor staging. GEPIA analysis was initially employed to analyze correlation of FOXPs and tumor immune infiltrating cells, and TIMER dataset was then included for standardization according to tumor purity. Result: Different member of FOXPs showed divergence in expression in various cancer tissues. Lower FOXP1, FOXP2 and higher FOXP3, FOXP4 levels could be identified in thyroid cancer tissues when compared with matched normal tissue. There was an inverse correlation between FOXP2, FOXP4 and immune invasion, whereas FOXP1 and FOXP3 were positively correlated. FOXPs showed remarkable correlations with multiply immune cells. More importantly, only FOXP2 showed the significant effect on recurrence and tumor staging. Conclusion: As immune regulatory factor, the reduction of FOXP2 may affect tumor microenvironments and immune cells infiltration, enhance tumor immune escape, and promote recurrence of thyroid cancer. FOXP2 could be a new potential diagnostic and prognostic marker.

Risks of central lymph node metastasis in papillary thyroid carcinoma with or without multifocality in at least one lobe: A multi-center analysis.

PURPOSES: To quantitatively predict central lymph node metastasis (CLNM) risks by comparing the clinicopathological features of different multifocal manifestations in papillary thyroid carcinomas (PTC) patients. METHODS: A total of 998 PTC patients from three medical centers were retrospectively analyzed. RESULTS: PTC patients with multifocal lesions in at least one thyroid lobe (MF group) yielded significantly higher CLNM rates than those with unifocal lesions in one or both lobes (UF group). Multifocality in at least one lobe rather than bilateral presence was confirmed to be an independent risk factor of CLNM for PTC patients. Four (age, gender, maximum tumor diameter, and thyroid capsular invasion (TCI)) and three (age, gender, and TCI) factors were proven to be independent risk factors of CLNM for patients within UF and MF groups, respectively. Predictive nomograms were established for these patients based on their respective high-risk factors. The accuracy and validity of these newly-created models were verified using C-index and calibration curves. Patients within UF and MF groups possessing significantly different CLNM risks based on individualized nomogram risk scores were further classified into different subgroups. A detailed CLNM risk stratification flow chart covering all PTC patients was then established. CONCLUSION: A meticulous evaluating system that quantifiesCLNM risk for PTC patients with unifocal lesions in one or both lobes and multifocal lesions in at least one lobe was established.

Lateral Involvement in Different Sized Papillary Thyroid Carcinomas Patients with Central Lymph Node Metastasis: A Multi-Center Analysis.

Objective: To quantitatively predict the probability of lateral lymph node metastasis (LLNM) for papillary thyroid carcinomas (PTC) patients with central lymph node metastasis (CLNM) in order to guide postoperative adjuvant treatment. Methods: Five hundred and three PTC patients with CLNM from three medical centers were retrospectively analyzed. Results: The LLNM rate for all patients was 23.9% (120 in 503), with 15.5% (45 in 291) and 35.4% (75 in 212) for patients with papillary thyroid microcarcinoma (PTMC) and large papillary thyroid carcinoma (LPTC), respectively. Patients with no fewer than five positive central lymph nodes (CLN) exhibited a higher risk of LLNM. For patients with fewer than five positive CLN, a maximum diameter of positive CLN > 0.5 cm and the presence of ipsilateral nodular goiter were identified as independent risk factors of LLNM for papillary thyroid microcarcinoma (PTMC) patients. The independent risk factors of LLNM for large papillary thyroid carcinoma (LPTC) patients included a tumor located in the upper portion of thyroid, maximum tumor diameter ≥ 2.0 cm, maximum diameter of positive CLN > 0.5 cm, and the presence of thyroid capsular invasion. Predictive nomograms were established based on these risk factors for PTMC and LPTC patients, respectively. The accuracy and validity of our newly built models were verified by C-index and calibration curves. PTMC and LPTC patients with fewer than five positive CLN were each stratified into three subgroups based on their nomogram risk scores, and a detailed risk stratification flow chart was established for a more accurate evaluation of LLNM risk in PTC patients. Conclusions: A detailed stratification flow chart for PTC patients with CLNM to quantitatively assess LLNM risk was established, which may aid in clinical decision-making for those patients.

An integrated bioinformatic investigation of mitochondrial energy metabolism genes in colon adenocarcinoma followed by preliminary validation of CPT2 in tumor immune infiltration.

Background: The prognosis for colon adenocarcinoma (COAD) today remains poor. Changes in mitochondria-related genes and metabolic reprogramming are related to tumor growth, metastasis, and immune evasion and are key factors in tumor genesis and development. Methods: TCGA database was used to analyze the differentially expressed mitochondrial energy metabolism pathway-related genes (MMRGs) in COAD patients, and the mutation of MMRG in tumor cells, the biological processes involved, and the correlation with tumor immunity were also analyzed. Then, MMRG and MMRG-related genes were used to divide COAD patients into different subtypes, and immunocorrelation analysis and survival analysis were performed. Finally, univariate regression analysis and LASSO regression analysis were used to construct a prognostic risk model for COAD patients, which was verified by the GEO database and evaluated by Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves, and the correlation between the risk model and immunity and clinical subtypes based on MMRG was analyzed. Results: In this study, the MMRG patterns and tumor immune microenvironment characteristics in COAD patients were systematically evaluated by clustering the expression of 188 MMRGs. We identified two subtypes of COAD with different clinical and immunological characteristics. Eight of the 28 differentially expressed MMRG genes were used to construct risk scores. ROC and K-M curves suggested that the risk model could well predict the prognosis of COAD patients, and the risk model was related to immune cell infiltration and immune function. Conclusions: The two COAD subtypes identified by MMRG are helpful for the clinical differentiation of patients with different prognoses and tumor progressions, and the risk score can assist the clinical evaluation of patient prognosis. Our results suggest that CPT2 contributes to the recruitment and regulation of neutrophils in COAD. CPT2 may act as a valuable biomarker for COAD immunotherapy.

Cervical Lymph Node Metastasis Differences in Patients with Unilateral or Bilateral Papillary Thyroid Microcarcinoma: A Multi-Center Analysis.

Purposes: To quantitatively predict the risk of neck lymph node metastasis for unilateral and bilateral papillary thyroid microcarcinomas (PTMC) that may guide individual treatment strategies for the neck region. Methods: A total of 717 PTMC patients from three medical centers were enrolled for analysis. Results: Bilateral PTMCs were demonstrated to be more aggressive with a much higher cervical lymph node metastasis rate including for both central (CLNM) and lateral lymph node metastasis (LLNM) when being compared to unilateral PTMCs. In unilateral PTMC, five (age < 55 years old, male, maximum tumor diameter (MTD) ≥ 0.5 cm, and the presence of thyroid capsular invasion (TCI) and multifocality) and three (maximum diameter of positive CLN (MDCLN) > 0.5 cm, the presence of multifocality and nodular goiter, iNG) factors were identified as independent risk factors for CLNM and LLNM, respectively. In bilateral PTMC, three (age < 55 and presence of TCI and multifocality in at least one side of thyroid lobe) and two (MDCLN > 0.5 cm and presence of nodular goiter (iNG)) factors were identified as independent factors for CLNM and LLNM, respectively. Predictive models of CLNM and LLNM for patients with unilateral disease and of CLNM for patients with the bilateral disease were established based on the described risk factors. Bilateral patients with positive CLNM were also stratified into different subgroups according to the presence and absence of independent risk factors. Conclusion: An evaluation system based on independent factors of CLNM and LLNM for PTMC patients with bilateral and unilateral disease was established. Our newly established evaluation system can efficaciously quantify risks of CLNM and LLNM for PTMC patients with bilateral and unilateral disease and may guide individual treatment strategy including both surgical and postoperative adjuvant treatment of the neck region for these patients.

Examining the association between serum IgG of oral bacteria and metabolic syndrome.

Aim: This investigation explored the relationship between oral bacteria and metabolic syndrome (METS). Materials and Methods: There were 4,882 subjects enrolled in this cross-sectional study from the NHANES III database. The severity of periodontitis was classified into mild, moderate and severe. We measured oral bacterial antibodies. We examined the relationship between serum immunoglobulin G (IgG) antibodies of oral bacteria and METS via performing multivariate regression analysis. Mediation analysis of oral bacteria on the correlation between periodontitis and METS was also executed. Results: After adjusting for covariates, the serum IgG antibodies of P. nigrescens, E. corrodens, and E. nodatum were associated with the presence of METS (p = 0.006, p = 0.014 and p = 0.018, respectively). Furthermore, serum IgG antibodies of P. intermedia, T. forsythia and V. parvula were positively associated with the presence of METS (p = 0.001, p = 0.011, and p = 0.002, respectively) and ≥4 features of METS (p = 0.019, p = 0.025, and p = 0.02, respectively). P. intermedia IgG mediated 11.2% of the relationship between periodontitis and METS. Conclusion: Serological markers of oral pathogens were correlated with the presence and the number of METS features after multivariable adjustment. Oral bacteria acted as a mediator of the correlation between periodontitis and METS. Our study provided a biologically plausible explanation for the association between periodontitis and METS, which provides a comprehensive evaluation of periodontitis.

A framework for the general design and computation of hybrid neural networks.

There is a growing trend to design hybrid neural networks (HNNs) by combining spiking neural networks and artificial neural networks to leverage the strengths of both. Here, we propose a framework for general design and computation of HNNs by introducing hybrid units (HUs) as a linkage interface. The framework not only integrates key features of these computing paradigms but also decouples them to improve flexibility and efficiency. HUs are designable and learnable to promote transmission and modulation of hybrid information flows in HNNs. Through three cases, we demonstrate that the framework can facilitate hybrid model design. The hybrid sensing network implements multi-pathway sensing, achieving high tracking accuracy and energy efficiency. The hybrid modulation network implements hierarchical information abstraction, enabling meta-continual learning of multiple tasks. The hybrid reasoning network performs multimodal reasoning in an interpretable, robust and parallel manner. This study advances cross-paradigm modeling for a broad range of intelligent tasks.

Clinicopathological Findings Associated With Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Retrospective Study in China.

OBJECTIVE: The incidence of papillary thyroid microcarcinoma (PTMC) has increased sharply during the past decades. Yet, whether or not nodal dissection should be performed remains controversial. This article aims to assess the high-risk factors associated with cervical lymph node metastasis (LNM) in patients with PTMC, which may potentially guide clinical management decision-making. METHODS: Medical records of 449 PTMC patients who underwent thyroidectomy in our hospital from August 2016 to July 2017 were retrospectively reviewed. Clinical and pathological factors of the patients were anonymously extracted from the charts and analyzed. RESULT: The patients were classified into two subgroups according to maximum tumor size measured through post-surgical pathology: smaller PTMC group (≤5 mm) and larger PTMC group (>5 mm). Larger tumor size was found to be associated with a higher rate of LNM (P = .001), particularly central lymph node metastasis (CLNM) (P = .001). Tumor size was also associated with extrathyroidal tumor extension (ETE) (P < .001), bilateral lesions (P = .015), and BRAFv600e mutation (P = .004). LNM was found to be more common in older patients (>55 y) (P = .030), and those with multifocal cancer (P < .001). In PTMC patients with unilateral lesions without ETE, tumor size was not significantly associated with LNM (P = .121). CONCLUSIONS: For the PTMC population, tumor size was an independent risk factor for LNM, particularly for patients of old age (>55 y), and multifocality. However, in PTMC patients with unilateral lesions without extrathyroidal extension, tumor size was not related to the risk of LNM. These findings may potentially guide clinical decision-making in terms of cervical nodal dissection.

Serum 25-hydroxyvitamin D level is unreliable as a risk factor and prognostic marker in papillary thyroid cancer.

Background: Low levels of vitamin D and altered local vitamin D metabolism have been associated with the prevalence and aggressiveness of several cancers. However, the effect of vitamin D on papillary thyroid cancer (PTC) is controversial. This study aimed to evaluate the impact of preoperative serum vitamin D levels and local vitamin D metabolism on the clinicopathologic characteristics and prognosis of PTC. Methods: In total, 1,578 patients with PTC and 128 patients with benign thyroid diseases were included. Clinical and pathologic data were analyzed to evaluate the role of vitamin D as a risk factor and prognostic marker in PTC. Moreover, a tissue microarray was used to investigate the role of local vitamin D metabolism in PTC progression. Results: Participants with PTC were younger compared to those with benign disease. No significant differences in 25-hydroxy vitamin D [25(OH)D] levels were observed between benign and malignant cases. Among patients with PTC, analyses of prognostic features revealed that decreased 25(OH)D levels were not overtly associated with poor prognosis in PTC. Additionally, local vitamin D metabolism was not associated with the aggressiveness of PTC. Conclusions: Serum 25(OH)D determination may not contribute to risk assessment workup of thyroid nodules. Moreover, decreased preoperative serum vitamin D and local vitamin D metabolism were not associated with poor prognosis of PTC.

The central role of a two-way positive feedback pathway in molecular targeted therapies-mediated pyroptosis in anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive tumours. We previously confirmed that apatinib has potential therapeutic effects on ATC via regulated cell death (RCD). As a newly identified RCD, pyroptosis demonstrates direct antitumour activity different from apoptosis or autophagy. Therefore, the clinical significance, regulatory role and underlying mechanisms of pyroptosis in ATC were focused on in this study. METHODS: In a phase II trial, patients with anaplastic or poorly differentiated thyroid carcinoma received apatinib 500 mg once daily. Multiple assays were implemented to evaluate the antitumour efficacy of apatinib and/or melittin in vitro and in vivo. High-throughput sequencing was applied to analyse differential mRNAs expression in ATC cells treated by apatinib with or without melittin. In situ Hoechst 33342/PI double-staining, LDH release assay and enzyme-linked immunosorbent assay (ELISA) were employed to determine pyroptosis. In mechanism exploration, quantitative RT-PCR, Western blotting and si-RNA knocking down were executed. RESULTS: Seventeen patients were evaluable. Apatinib showed a promising therapeutic effect by a disease control rate (DCR) of 88.2%; however, treatment was terminated in 23.5% of patients due to intolerable toxicity. To reduce adverse events, a pyroptosis-mediated synergistic antitumour effect of apatinib and melittin was identified in treatment of ATC in vitro and in vivo. The caspase-1-gasdermin D (GSDMD) axis-mediated pyroptosis was the key to extra antitumour effect of the combination of apatinib and melittin. Moreover, caspase-3-gasdermin E (GSDME) pyroptosis pathway also functioned importantly in addition to caspase-1-GSDMD pathway. Evidenced by in vitro and in vivo study, a two-way positive feedback interaction was innovatively confirmed between caspase-1-GSDMD and caspase-3-GSDME axes. CONCLUSIONS: Through pyroptosis mediated by caspase-1-GSDMD and caspase-3-GSDME axes synchronically, low-dosage apatinib and melittin could synergistically achieve a comparable therapeutic potential with reduced AEs. More importantly, a two-way positive feedback interaction is innovatively proposed between these two axes, which provide a new prospect of targeted therapy.

Prognostic significance of subjective oral dysfunction on the all-cause mortality.

BACKGROUND: As the proportion of elderly population grows, it raises concern about impaired oral health which has been reported to be associated with increased risk of numerous adverse health events. Emerging study defined oral frailty as poor oral health accumulation and demonstrated that oral frailty was a risk factor of disability, physical frailty and mortality. In this study, we examined the association between subjective oral dysfunction and all-cause mortality in the United States. METHODS: In this cross-sectional observational study, a total of 7827 participants who completed oral functions data from 1999 to 2002 NHANES database were recruited. Subjective oral dysfunction included 3 components: limited eating ability, dry mouth and difficult swallowing, which were obtained from self-reported questionnaire. For primary outcome, all-cause mortality was followed from baseline to death or 2006. The relationship of subjective oral dysfunction and all-cause mortality was assessed by Cox regression model. RESULTS: A statistically significant relationship between subjective oral dysfunction and all-cause mortality was observed in fully adjusted model. Participants with more components of subjective oral dysfunction had worse risk of all-cause mortality. Limited eating ability was inversely associated with muscle strength. CONCLUSION: Subjective oral dysfunction which was obtained from an easy self-assessment survey might be a potential risk factor for all-cause mortality and could be used for initial screening during general health examination.

Exploring the relationship between trans fatty acids and body fat distribution.

INTRODUCTION: The importance of fat distribution is well established. Nevertheless, the mechanism by which fat is distributed throughout the trunk and limbs remains unclear. OBJECTIVES: The aim of this study was to uncover the relationship between 4 trans fatty acids (TFAs) and body fat distribution in the trunk and limbs. PATIENTS AND METHODS: The study examined 1467 participants registered in the National Health and Nutrition Examination Survey database between 1999 and 2000. A cross­sectional analysis was conducted to evaluate the relationship between TFA and body fat distribution over the trunk and limbs. RESULTS: In the unadjusted model for men, trunk fat percentage was significantly associated with trans 9­hexadecenoic acid (ß = 0.250; 95% CI, 0.187-0.313; P <0.01), trans 11­octadecenoic acid (ß = 0.927; 95% CI, 0.499-1.356; P <0.01), trans 9­octadecenoic acid (ß = 1.028; 95% CI, 0.654-1.402; P <0.01), and trans 9, trans 12­octadienoic acid (ß = 0.078; 95% CI, 0.054-0.103; P <0.01). No significant association was found between limb fat percentage and TFA. CONCLUSIONS: Our study demonstrated that increased TFA concentration was associated with fat deposition predominantly in the trunk rather than in the limbs. Further research is needed to investigate the role of TFA in different body fat distributions.

Seismic Behavior of Stone Masonry Joints with ECC as a Filling Material.

This paper investigates the seismic behavior of novel stone masonry joints using ductile engineered cementitious composite (ECC) as a substitute for ordinary mortar. Ten stone masonry joints with different types of mortar/ECC were tested under axial and cyclic loads. The filling materials of mortar joints tested included ordinary mortar, polymer mortar, ECC, and composite mortar with two combination proportions of ECC and ordinary mortar. The test results indicated that ECC specimens exhibited a more stable hysteretic response as well as an improvement in strength, deformation, energy dissipation, and strength degradation. The ECC mortar joints maintained integrity during the entire loading process due to the "self-confinement" effect of ECC. A partial substitution of mortar with ECC could provide effective reinforcement and confinement to prevent mortar failure and peeling, thereby allowing such specimens to approach the seismic performance of ECC specimens. Based on the trend of shear strength variations, a corresponding failure process is defined for ECC/mortar joints under cyclic and axial compressive loads, including four distinct stages: linear elastic, crack-developing stage, interface debonding, and friction sliding. New equations are proposed for predicting the shear strength and residual shear strength of the ECC/mortar joints on the basis of the test results, which are validated in the composite mortar specimens.