Quantitative parameter analysis of pretreatment dual-energy computed tomography in nasopharyngeal carcinoma cervical lymph node characteristics and prediction of radiotherapy sensitivity.

BACKGROUND: Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor-node-metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck-lymph node radiotherapy in patients with NPC. METHODS: Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. RESULTS: DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73-0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. CONCLUSION: Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

Enhancing ECG heartbeat classification with feature fusion neural networks and dynamic minority-biased batch weighting loss function.

OBJECTIVE: This study aims to address the challenges of imbalanced heartbeat classification using electrocardiogram (ECG). In this proposed novel deep-learning method, the focus is on accurately identifying minority classes in conditions characterized by significant imbalances in ECG data. Approach: We propose a Feature Fusion Neural Network enhanced by a Dynamic Minority-Biased Batch Weighting Loss Function. This network comprises three specialized branches: the Complete ECG Data Branch for a comprehensive view of ECG signals, the Local QRS Wave Branch for detailed features of the QRS complex, and the R Wave Information Branch to analyze R wave characteristics. This structure is designed to extract diverse aspects of ECG data. The dynamic loss function prioritizes minority classes while maintaining the recognition of majority classes, adjusting the network's learning focus without altering the original data distribution. Together, this fusion structure and adaptive loss function significantly improve the network's ability to distinguish between various heartbeat classes, enhancing the accuracy of minority class identification. Main Results: The proposed method demonstrated balanced performance within the MIT-BIH dataset, especially for minority classes. Under the intra-patient paradigm, the accuracy, sensitivity, specificity, and positive predictive value (PPV) for Supraventricular ectopic beat were 99.63%, 93.62%, 99.81%, and 92.98%, respectively, and for Fusion beat were 99.76%, 85.56%, 99.87%, and 84.16%, respectively. Under the inter-patient paradigm, these metrics were 96.56%, 89.16%, 96.84%, and 51.99% for Supraventricular ectopic beat, and 96.10%, 77.06%, 96.25%, and 13.92% for Fusion beat, respectively. Significance: This method effectively addresses the class imbalance in ECG datasets. By leveraging diverse ECG signal information and a novel loss function, this approach offers a promising tool for aiding in the diagnosis and treatment of cardiac conditions. .

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy. MATERIALS AND METHODS: The observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed. RESULTS: Moderate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS. CONCLUSION: Radiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

Prediction of severe radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma using the combined systemic immune-inflammatory index and prognostic nutritional index.

OBJECTIVE: Severe radiation-induced oral mucositis (sRIOM) can seriously affect patients' quality of life and treatment compliance. This study was to investigate the utility of the systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in predicting sRIOM in patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: 295 patients with LANPC were retrospectively screened. The pre-radiotherapy SII and PNI were calculated based on peripheral blood samples. A receiver operating characteristic (ROC) curve was used to determine the cut-off value. Logistic regression was used for univariate and multivariate analyses. Patients were classified into three groups based on the SII-PNI score: score of 2, high SII (> cut-off value) and low PNI (≤ cut-off value); score of 1, either high SII or low PNI; score of 0, neither high SII nor low PNI. RESULTS: The SII-PNI demonstrated significant predictive ability for sRIOM occurrence, as evidenced by an area under the curve (AUC) of 0.738. The incidence rates of sRIOM with SII-PNI score of 2, 1, and 0 were 73.86%, 44.35%, and 18.07%, respectively. Multivariate analysis confirmed that the SII-PNI score was an independent risk factor for sRIOM. CONCLUSION: The SII-PNI score is a reliable and convenient indicator for predicting sRIOM in patients with LANPC.

Polyphenolic Platform Ameliorated Sanshool for Skin Photoprotection.

Natural evolution has nurtured a series of active molecules that play vital roles in physiological systems, but their further applications have been severely limited by rapid deactivation, short cycle time, and potential toxicity after isolation. For instance, the instability of structures and properties has greatly descended when sanshool is derived from Zanthoxylum xanthoxylum. Herein, natural polyphenols are employed to boost the key properties of sanshool by fabricating a series of nanoparticles (NPs). The intracellular evaluation and in vivo animal model are conducted to demonstrate the decreased photodamage score and skin-fold thickness of prepared NPs, which can be attributed to the better biocompatibility, improved free radical scavenging, down-regulated apoptosis ratios, and reduced DNA double-strand breaks compared to naked sanshool. This work proposes a novel strategy to boost the key properties of naturally occurring active molecules with the assistance of natural polyphenol-based platforms.

A risk model for the early diagnosis of acute myocardial infarction in patients with chronic kidney disease.

Introduction: Acute myocardial infarction (AMI) remains a critical disease, characterized by a high fatality rate in several countries. In clinical practice, the incidence of AMI is increased in patients with chronic kidney disease (CKD). However, the early diagnosis of AMI in the above group of patients is still poor. Methods: In the present study, a total of 829 patients with CKD, defined by an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 or 60-90 ml/min/1.73 m2 for patients with mildly reduced kidney function, who attended the Sichuan Provincial People's Hospital (SPPH) between January 2018 and November 2022 were enrolled. All patients underwent coronary angiography due to the presence of typical or atypical symptoms of AMI. Patients were divided into the following two groups: The training cohort, including 255 participants with AMI and 242 without AMI; and the testing cohort, including 165 and 167 subjects with and without AMI, respectively. Furthermore, a forward stepwise regression model and a multivariable logistic regression model, named SPPH-AMI-model, were constructed to select significant predictors and assist the diagnosis of AMI in patients with CKD, respectively. Results: The following factors were evaluated in the model: Smoking status, high sensitivity cardiac troponin I, serum creatinine and uric acid levels, history of percutaneous coronary intervention and electrocardiogram. Additionally, the area under the curve (AUC) of the receiver operating characteristic curve were determined in the risk model in the training set [AUC, 0.78; 95% confidence interval (CI), 0.74-0.82] vs. the testing set (AUC, 0.74; 95% CI, 0.69-0.79) vs. the combined set (AUC, 0.76; 95% CI, 0.73-0.80). Finally, the sensitivity and specificity rates were 71.12 and 71.21%, respectively, the percentage of cases correctly classified was 71.14%, while positive and negative predictive values of 71.63 and 70.70%, respectively, were also recorded. Discussion: The results of the current study suggested that the SPPH-AMI-model could be currently considered as the only risk scoring system for the early diagnosis of AMI in patients with CKD. This method could help clinicians and emergency physicians to quickly and accurately diagnose AMI in patients with CKD to promote the immediate and effective treatment of these patients.

Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients Treated with Definitive Chemoradiotherapy for Locally Advanced Oesophageal Squamous Cell Carcinoma.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been shown to have prognostic value in several common cancers. This study aimed to investigate the prognostic value of NLR in patients with advanced oesophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT). Methods: A retrospective analysis was performed on 158 patients with advanced ESCC who received dCRT from January 2012 to December 2018. The NLR for different treatment stages was calculated based on laboratory test results. The Kaplan-Meier (KM) method and Cox proportional regression model were used to analyse the relationship between NLR and overall survival (OS). Results: The mean NLR of 158 patients with ESCC was 3.403 ± 2.479. The pre-treatment NLR cut-off was 4.839, and patients were divided into the low NLR group (NLR < 4.839) and the high NLR group (NLR ≥ 4.839). NLR in patients with ESCC was related to N stage (P < 0.05). The KM analysis showed that the median OS of all enrolled patients was 29.3 months, the median OS periods of patients in the high and low NLR groups were 15.6 and 35.8 months, respectively, and the OS of the low NLR group was better than that of the high NLR group (P < 0.001). In the multivariate analysis, NLR was an independent prognostic factor that affects the prognosis of patients with ESCC receiving dCRT. Furthermore, patients who maintained a high NLR before and after treatment showed worse clinical outcomes than the other groups. Conclusion: Our findings suggest that NLR can effectively assess the prognosis of patients with advanced ESCC undergoing dCRT.

Prognostic value of the cervical lymph node necrosis ratio in nasopharyngeal carcinoma.

PURPOSE: Whether cervical lymph node necrosis (CNN) is an independent adverse prognostic factor in nasopharyngeal carcinoma (NPC) has not been determined. In this study, the CNN ratio was graded quantitatively to explore the prognostic value in NPC. PARTICIPANTS AND METHODS: We retrospectively reviewed a total of 648 pathologically confirmed as NPC. We outlined metastatic lymph nodes and necrotic area of lymph nodes slice by slice on the magneticresonanceimages (MRI) cross section, and calculated the corresponding CNN ratio. RESULTS: The median CNN ratio (17.37 %) was taken as the cut-off point, 256 (39.51 %) patients were divided into CNN1 group (<17.37 %, n = 128) and CNN2 group (≥17.37 %, n = 128), 392 (60.49 %) patients without lymph nodes necrosis were CNN0. Among the CNN0, CNN1 and CNN2 groups, five-year overall survival (OS) was 82.4 %, 76.6 % and 71.1 %, locoregional recurrence-free survival (LRRFS) was 91.3 %, 91.1 % and 90.5 %, distant metastasis-free survival (DMFS) was 83.7 %, 78.5 % and 68.7 %, progression-free survival (PFS) was 78.3 %, 71.7 % and 61.6 % respectively. By multivariate analysis, CNN was an independent prognostic factor for OS (P = 0.003), DMFS (P = 0.019) and PFS (P = 0.007). More than 3 cycles of chemotherapy significantly increased OS (P = 0.024) and DMFS (P = 0.015) in the CNN1 group. CONCLUSIONS: This study indicated that CNN is one of the factors with the negative prognosis of NPC. The CNN ratio might be used as one of the reference factors in the formulation of individualized treatment plan.

Comparing the efficacy and safety of cisplatin and other platinum-based chemotherapies in locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). However, the side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapies in the treatment of NPC. We performed a meta-analysis to compare the efficacy and safety of cisplatin-based regimens and other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using Review Manager Software version 5.4. RESULTS: A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, were equivalent in both groups. However, the incidence of anemia was higher in patients receiving other platinum-based chemotherapies. The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and late side effects between the two groups. CONCLUSIONS: Other types of platinum-based chemotherapies are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed.

A Novel Electrocardiography Model for the Diagnosis of Acute Pulmonary Embolism.

Acute pulmonary embolism (acPE) is a severe disease that is often misdiagnosed as it is difficult to detect quickly and accurately. In this study, a novel electrocardiogram (ECG) model was used to estimate the probability of acPE rapidly via analysis of ECG characteristics. A total of 327 patients with acPE who were diagnosed at the Sichuan Provincial People's Hospital (SPPH) between 2018 and 2021 were retrospectively studied. A total of 331 patients were randomly selected as the control group, which included patients hospitalized during the same time period. The control group included patients who presented with characteristic symptoms of acPE, but this diagnosis was ruled out following further diagnostic testing. This study compared the diagnostic value of the ECG model with those of another ECG scoring model (Daniel-ECG score) and the most common prediction models (Wells score and Geneva score). This study established an ECG-predictive model using analysis of the ECG abnormalities in patients with acPE. The final ECG model included certain novel ECG signs that had not been incorporated in the previous ECG score of the patients, and thus, compared to the previous ECG score, exhibited a more favorable area under the receiver operating characteristic curve (AUC) value (0.8741). The model developed in this study was named the SPPH-ECG model. Furthermore, this study compared the SPPH-ECG model with Daniel-ECG score, Wells score, and Geneva score, and the SPPH-ECG model was demonstrated to exhibit a superior AUC value (0.8741), sensitivity (79.08%), negative predictive value (79.52%), and test accuracy (79.42%), while the Geneva score presented superior specificity (100%) and positive predictive value (100%) compared with the SPPH-ECG model. In conclusion, the SPPH-ECG model may play a role in ruling out acPE in patients during diagnostic testing and diagnose acPE rapidly and accurately in combination with the Geneva scoring system.

Effects of different drugs on the curative effect, stress responses, and the circulatory system of patients with hypertensive trigeminal neuralgia.

BACKGROUND: This research aimed to analyze the effects of stellate nerve block with different drugs on the curative effect, stress responses, and the circulatory system of patients with hypertensive trigeminal neuralgia (TN). METHODS: A retrospective analysis of 82 patients with hypertensive TN admitted to our hospital from January 2019 to January 2021 was conducted, and the patients were divided into a control group and an observation group according to different drugs. The pain visual analogue scale (VAS) scores were determined between the 2 groups before treatment and at 1, 2, 3, 7, and 30 d after treatment. The mean arterial pressure (MAP) and heart rate (HR) were measured in the 2 groups of patients before treatment and immediately after treatment (T0), half an hour after treatment (T1), 1 h after treatment (T2), and 6 h after treatment (T3). The left ventricular wall thickness (LVWT), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and fraction shortening (FS) were detected in the 2 groups before treatment and at T0-T2. Patient satisfaction was also scored, and the incidence of adverse reactions was assessed. RESULTS: The VAS scores of the 2 groups of patients decreased significantly after treatment at 1, 2, 3, 7, and 30 d. The MAP and HR indicators of the 2 groups decreased gradually at T0-T2, and gradually recovered to levels before treatment at the T3 time point. The MAP and HR indicators of the observation group were significantly lower than those of the control group at T0-T2. After treatment, the levels of LVWT, LVESV, LVEF, and FS in the observation group at the T0-T2 time points were significantly lower than those of the control group. Additionally, after treatment, the satisfaction of the observation group was significantly higher than that of the control group. The total incidence of adverse reactions in the observation group was significantly lower than that in the control group. CONCLUSIONS: For patients with hypertensive TN, a single ropivacaine stellate nerve block can significantly relieve pain, and has little effect on heart function.

miR-498 inhibits autophagy and M2-like polarization of tumor-associated macrophages in esophageal cancer via MDM2/ATF3.

Structured abstract Aim: To elucidate the effect of miRNA (miR)-498 on autophagy and M2-like macrophage polarization in esophageal cancer. Methods: Autophagy was evaluated in esophageal cancer. Macrophage markers specific for M1- or M2-like phenotype were determined. The binding relationships between miR-498 and MDM2, MDM2 and ATF3 were analyzed. Results: miR-498 was downregulated in esophageal cancer and was associated with disease-free and overall patient survival. Enhanced miR-498 reduced LC3I conversion to LC3II and increased p62 accumulation in KYSE-150 cells, and increased macrophage polarization to M2-like phenotype in KYSE-150 and TAM co-culture. miR-498 inhibited MDM2-mediated ATF3 degradation, thus suppressing autophagy and M2-like polarization of macrophages in esophageal cancer. Conclusion: miR-498 may inhibit autophagy and M2-like polarization of macrophages to suppress esophageal cancer via MDM2/ATF3.

Lay abstract In this study, we aimed to elucidate the therapeutic mechanism of miRNA (miR)-498 in autophagy and macrophage polarization to M2-like phenotype in esophageal cancer. This study reports lower miR-498 expression in esophageal cancer tissues compared with adjacent normal tissues. According to the experimental results, miR-498 negatively targets MDM2 by binding to its 3'UTR, which leads to attenuated ubiquitination and degradation of ATF3 induced by MDM2. Specifically, overexpressed miR-498 reduces ratio of LC3II (a marker that is commonly utilized to detect cell autophagy) to LC3I and increases p62 (a common cargo receptor for autophagy) accumulation in KYSE-150 cells, and elevates macrophage polarization to M2-like phenotype by depressing MDM2-mediated ATF3 degradation. The present study deepened our understanding of the causes of esophageal cancer and provided at least three novel therapeutic targets for the development of effective targeted therapy for esophageal cancer.

Silence of lncRNA MIAT-mediated inhibition of DLG3 promoter methylation suppresses breast cancer progression via the Hippo signaling pathway.

As the foremost common female malignancy, breast cancer (BC) poses a significant public health stumbling block. Although treatment protocols have improved over the years, the overall prognosis of BC remains unsatisfactory. Extensive investigations have taken place into long non coding RNAs (lncRNAs) pertaining to their involvement in carcinogenesis. The current study in connection with bioinformatics tools aimed to identify the myocardial infarction associated transcript (MIAT) as a BC-related differentially expressed lncRNA in an attempt to elucidate the effect of MIAT in BC cells. MIAT was initially overexpressed while DLG3 was down-regulated in BC. BC cells were subsequently treated with si-MIAT or/and si-DLG3, after which the expressions of DLG3 and the Hippo signaling pathway-related proteins were evaluated to analyze their regulatory mechanism in BC, which indicated that MIAT inhibition up-regulated DLG3 and activated the Hippo signaling pathway to suppress proliferation and promote apoptosis of BC cells. MS-PCR and RIP assays demonstrated that MIAT bound to the methylation proteins DNMT1, DNMT3A and DNMT3B, promoted the methylation of CpG islands in DLG3 promoter and inhibited the DLG3 expression. Moreover, our data suggested that DLG3 could bind to MST2 and regulate LAST1, which prevented the nuclear translocation of YAP. The in vitro results were further verified via the in vivo findings. Taken together, the central findings of our study demonstrate that MIAT silencing inhibits BC progression by means of up-regulating DLG3 via activation of the Hippo signaling pathway, highlighting a novel potential therapeutic target for the treatment of the BC.

Remifentanil attenuates cardiac dysfunction, lipid peroxidation and immune disorder in rats with isoproterenol-induced myocardial injury via JNK/NF-KB p65 inhibition.

BACKGROUND: Myocardial injury caused by myocardial ischemia (MI) is still a severe condition that can result in apoptosis, oxidative stress, and inflammation. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. It can improve sinusoidal heart rate patterns in the fetus, for bupivacaine-induced cardiotoxicity, and with lipopolysaccharide (LPS)-induced cardiomyocytes injuries. This study aimed to explore the cardioprotective effects of remifentanil in MI model rats. METHODS: Sprague Dawley (SD) rats were split into five groups at random, including a control group, Isop group, low-dose remifentanil treatment group (10 µg/kg), medium-dose remifentanil treatment group (20 µg/kg), and a high-dose remifentanil treatment group (40 µg/kg). The MI model was achieved by subcutaneously injecting rats with isoproterenol (85 mg/kg) for two consecutive days. With the expression of apoptotic molecules, myocardial systolic function index, inflammation, antioxidant enzymes, and the myocardial enzyme taken into account, the data was analyzed. RESULTS: After treatment with remifentanil, the left ventricular wall thickness (LVWT), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), fraction shortening (FS), and heart rate (HR) were significantly increased in comparison with the Isop group. Creatine kinase-MB (CK-MB), Mb, and cTnl expressions were decreased. Meanwhile, the levels of cleaved caspase-3 and caspase-9 were decreased. Remarkably, the levels of reactive oxidative species (ROS), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were observed to be repressed, while the levels of superoxide dismutase (SOD) was significantly increased. More importantly, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and interferon (IFN)-γ were decreased. CONCLUSIONS: Remifentanil has significant potential as a therapeutic intervention strategy for ameliorating myocardial injury after MI and these findings provide the rationale for further clinical studies.

[Corrigendum] Effects of the Tangningtongluo formula as an alternative strategy for diabetics via upregulation of insulin receptor substrate-1.

Subsequently to the publication of this article, the authors have realized that Fig. 4 contained some incorrectly incorporated data panels; specifically, the A­d, B­b and B­c panels did not display the correct data. The revised version of Fig. 4 featuring the correct data for the A­d, B­b and B­c panels is shown on the next page. Note that these errors did not affect the overall conclusions reported in the paper. The authors apologize to the Editor of Molecular Medicine Reports and to readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 703­709, 2017; DOI: 10.3892/mmr.2017.6679].

Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma.

Background: Platinum compounds are commonly used for lung cancer treatment. However, the severe side effects and relatively poor prognosis limit their therapeutic effect. Therefore, developing novel platinum derivative and treatment strategy are critical for current lung cancer therapy. Methods: Flow cytometry, HMGB1 and ATP release, and immunoblotting were performed to evaluate the Oxaliplatin-induced immunogenic cell death (ICD) in two lung carcinoma cells. Vaccination approach and subcutaneous tumor models were created to analyze the tumor regression effect of Oxaliplatin. PD-L1 mRNA and protein levels were detected in LLC (Lewis lung carcinoma). Enhanced therapeutic efficacy of LLC was assessed by co-administration Oxaliplatin and aPD-L1 in murine lung tumor model. Results: Oxaliplatin induced robust ICD in LLC cells, activated dendritic cells (DCs, CD80+CD86+) and enhanced cytotoxic T cells (CD8+) in LLC tumor tissues, which resulted in tumor regression. Co-administration of Oxaliplatin and checkpoint inhibitor, aPD-L1, could enhance the therapeutic efficacy of LLC in murine lung carcinoma. Conclusion: This study reveals Oxaliplatin can induce robust ICD in tumor tissues and suppress tumor growth by activating DCs and enhancing T-cell infiltration. Notably, the Oxaliplatin-induced ICD provides an immunogenic microenvironment, which enhances the checkpoint inhibitor therapeutic efficacy of LLC.

[Relationship of OPRM1 118A/G gene polymorphism and oxycodone analygesic dose in paitents with cancer pain].

OBJECTIVE: To investigate the relationship between OPRM1 118A/G gene polymorphism and oxycodone analgesic dose in patients with cancer pain. METHODS: DNA sequencing was used to detect the genotypies of OPRM1 118 A/G site in 203 patients with moderate and severe cancer pain, and to compare the relationship between the pain degree and the dose of oxycodone at 3 and 30 days after treatment in patients with different genotypes. RESULTS: The fequencies of AA, AG and GG genotypes at the OPRM1 118 A/G site were 34.78%, 52.70%, and 12.52%, respectively. The dosage of oxycodone in GG genotype was significantly higher than that in AA genotype and AG genotype (15.44±10.19 vs. 10.25±4.53, 10.49±5.26; 89.15±27.69 vs. 43.59±12.19, 48.27±18.79) on the 3 and 30 day after treatment, difference was statistically significant (P< 0.05). CONCLUSION: For cancer pain patients with GG genotype of OPRM1 118A/G site, if they need to achieve the same analgesic effect as patients with AA and AG genotype, the dose of oxycodone should be increased.

In vitro and in vivo study of the expression of the Syk/Ras/c­Fos pathway in chronic glomerulonephritis.

Chronic glomerulonephritis (CGN) is the most common form of glomerular disease; however, its associated molecular mechanisms remain unclear. Spleen tyrosine kinase (Syk) is a key mediator of B­receptor signaling on the surface of inflammatory cells. The primary target for R406 is Syk. The aim of the present study was to investigate the molecular mechanisms involved in a rat model of CGN induced by adriamycin (ADR) and in the rat glomerular mesangial cell line, HBZY­1, stimulated by lipopolysaccharide (LPS). CGN was induced in the rat models by two intravenous injections of ADR into the tail: 3.5 mg/kg ADR was given on the first day and 3.0 mg/kg on the fourteenth day. HBZY­1 cells were incubated with 0.5 µg/ml LPS for 48 h. The pathological alterations in the kidney tissues were observed by hematoxylin and eosin staining. The 24 h urinary protein, blood urea nitrogen (BUN) and creatinine levels were measured using an automatic biochemistry analyzer. The mRNA expression levels of Syk, Ras, mitogen activated protein kinase kinase (MEK), extracellular signal regulated kinase (ERK)1/2 and c­Fos was measured by reverse transcription­quantitative polymerase chain reaction. Subsequently, the protein levels of phosphorylated (p)­Syk, Ras, p­MEK1/2, p­ERK1/2 and c­Fos were measured by western blot analysis. In the model group, 24 h urinary protein, BUN and creatinine levels were increased when compared with the normal group (P<0.05). In addition, compared with the normal group, the mRNA and protein levels of the Syk/Ras/c­Fos pathway components in vitro and in vivo were markedly increased, inhibiting the abnormal cell viability of mesangial cells. In conclusion, the results of the present study suggested a potential role for the Syk/Ras/c­Fos signaling pathway in CGN, which indicated the necessity for further investigation at the clinical level.