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Metabolic reprogramming is a hallmark of cancer. The“Warburg effect”, also known as aerobic glycolysis, is an essential part of metabolic reprogramming and a central contributor to cancer progression. Moreover, hypoxia is one of the significant features of pancreatic ductal adenocarcinoma (PDAC). Under hypoxic conditions, the “Warburg effect” occurs to meet the nutrient and energy demands of rapid genome replication, remodeling the tumor microenvironment (TME) and influencing tumor immunity. α-Enolase (ENO1) is a multifunctional protein, acting as a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid. ENO1 was found to be overexpressed in multiple types of cancers. Here, we investigated the role of ENO1 in modulating the PDAC microenvironment.Using bioinformatic analyses, we demonstrated that ENO1 was highly expressed in PDAC patients, which was related to a poor prognosis. In vitro, Eno1 knockdown resulted in reduced PDAC cell proliferation and colony formation, along with enhanced apoptosis in PDAC cells. In vivo, tumorigenesis was suppressed in mouse PDAC models by Eno1 knockdown. Flow cytometry analysis revealed that high expression of Eno1 altered the tumor immune microenvironment (TIME), particularly the impaired tumor infiltration and function of CD8+ T cells. Mechanistic studies revealed that ENO1 upregulated PD-L1 to prevent CD8+ T cells infiltration through the hypoxia-inducible factor (HIF)-1α signaling pathway, leading to PDAC progression.In conclusion, our findings indicate that ENO1 might serve as a potential biomarker for PDAC and a novel onco-immunotherapeutic target via its role in altering the TIME.

Purpose – Bolted joint is the most important connection method in aircraft composite/metal stacked connections due to its large load transfer capacity and high manufacturing reliability. Aircraft components are subjected to complex hybrid variable loads during service, and the mechanical properties of composite/metal bolted joint directly affect the overall safety of aircraft structures. Research on composite/metal bolted joint and their mechanical properties has also become a topic of general interests. This article reviews the current research status of aeronautical composite/metal bolted joint and its mechanical properties and looks forward to future research directions. Design/methodology/approach – This article reviews the research progress on static strength failure and fatigue failure of composite/metal bolted joint, focusing on exploring failure analysis and prediction methods from the perspective of the theoretical models. At the same time, the influence and correlation mechanism of hole-making quality and assembly accuracy on the mechanical properties of their connections are summarized from the hole-making processes and damage of composite/metal stacked structures. Findings – The progressive damage analysis method can accurately analyze and predict the static strength failure of composite/metal stacked bolted joint structures by establishing a stress analysis model combined with composite material performance degradation schemes and failure criteria. The use of mature metal material fatigue cumulative damage models and composite material fatigue progressive damage analysis methods can effectively predict the fatigue of composite/metal bolted joints. The geometric errors such as aperture accuracy and holes perpendicularity have the most significant impact on the connection performance, and their mechanical responses mainly include ultimate strength, bearing stiffness, secondary bending effect and fatigue life. Research limitations/implications – Current research on the theoretical prediction of the mechanical properties of composite/metal bolted joints is mainly based on ideal fits with no gaps or uniform gaps in the thickness direction, without considering the hole shape characteristics generated by stacked drilling. At the same time, the service performance evaluation of composite/metal stacked bolted joints structures is currently limited to static strength and fatigue failure tests of the sample-level components and needs to be improved and verified in higher complexity structures. At the same time, it also needs to be extended to the mechanical performance research under more complex forms of the external loads in more environments. Originality/value – The mechanical performance of the connection structure directly affects the overall structural safety of the aircraft. Many scholars actively explore the theoretical prediction methods for static strength and fatigue failure of composite/metal bolted joints as well as the impact of hole-making accuracy on their mechanical properties. This article provides an original overview of the current research status of aeronautical composite/metal bolted joint and its mechanical properties, with a focus on exploring the failure analysis and prediction methods from the perspective of theoretical models for static strength and fatigue failure of composite/metal bolt joints and looks forward to future research directions.

Background: The timing and incidence of recurrent bone metastasis (BM) after radical gastrectomy in patients with gastric cancer (GC) as well as the survival of these patients were not fully understood. The aim of this study was to analyze the data of an observational GC cohort and identify patients who underwent curative gastrectomy and had recurrent BM to describe and clarify the pattern and profile of BM evolution after surgery. Methods: Data were retrieved from a hospital-based GC cohort, and patients who underwent upfront radical gastrectomy were selected. The time points of specific organ metastatic events were recorded, and the person-year incidence rate of metastatic events was calculated. The latency period of BM events after gastrectomy was measured and compared with that of the other two most common metastatic events, liver metastasis (LM) and distant lymph node metastasis (LNM), using analysis of variance. Propensity score matching and subgroup analysis were used for sensitivity analysis. Results: A total of 1324 GC cases underwent radical gastrectomy between January 2011 and December 2021. Of these, 67 BM, 218 LM, and 248 LNM occurred before the last follow-up. The incidence of BM events was 1.7/100 person-years, which was approximately 3-fold lower than that of LM and distant LNM events (5.5 and 6.3 per 100 person-years, respectively). BM events had a significantly longer latency (median time, 16.5 months) than LM and LNM events (11.1 and 12.0 months, respectively). Recurrent BM led to a worse prognosis (median survival, 4.5 months) than those of LM and LNM events (median survival, 7.7 and 7.1 months, respectively). However, no difference in overall survival after gastrectomy was observed among the groups. Conclusions: Compared with other common metastatic events, BM in GC after gastrectomy is a late-onset event indicating poor survival. Trial registration: No. ChiCTR1800019978; http://www.chictr.org.cn/.

The extract of peanut shell extract (PSE) is firstly utilized as a novel eco-friendly corrosion inhibitor for the mitigation of corrosion on carbon steel in 0.5 M sulfuric acid medium. The corrosion inhibition performance and adsorption properties of PSE were researched via weight loss, electrochemical measurements and surface characterization analysis. It is demonstrated that the PSE acts as a mixed type inhibitor with a superb inhibition ability of 95 % with the addition of 300 mg/L PSE. The adsorption of the active ingredients in PSE on steel surface contributes to effective corrosion inhibition. The outstanding inhibition efficiency and straightforward extraction method with environment-friendly solvent convincingly demonstrate that the PSE possesses promising application prospects to be a novel eco-friendly corrosion inhibitor in industrial corrosion mitigation.

Abstract Background Gastric cancer liver metastasis (GCLM) patients usually accompany by abnormal serum liver function tests (LFTs) more or less; however, the prognostic value of LFTs is not fully understood. This study aimed to develop a liver chemistry score (LCS) based on LFTs and incorporate it into prognosis determination for GCLM patients who received palliative chemotherapy. Methods Data were derived from hospitalized GCLM patients in two general hospitals in China. LCS was generated based on the results of LFTs by LASSO regression. Cutoff value of the score was determined by restricted cubic spline. The score was then incorporated into Cox regression analysis to construct a predictive nomogram; the model was then evaluated internally and externally by AUC of time‐dependent receiver operating characteristic curves (ROC) and calibration curves. Results Three hundred and thirty‐six and 72 patients were included in development and validation cohort, respectively. LASSO regression analysis in development cohort finally reached a two‐parametric LCS calculated on AST and ALP levels as 0.03343515 × ln (AST, U/L) + 0.02687997 × ln (ALP, U/L), and 0.232 was set as optimal cutoff value. Patients in low (LCS

Flow accelerated corrosion (FAC) behavior of X65 steel gradual contraction pipe in high CO2 partial pressure environments was investigated by in situ dynamic high pressure electrochemical measurements with Ag/AgCl reference electrode in FAC loop and microscopic characterization analysis. The corrosion rates in dynamic high CO2 partial pressure environments are obviously enhanced compared with those in dynamic atmospheric pressure and static high pressure environments. The FAC mechanism at gradual contraction pipe in high pressure environments exhibits significant distinction from that in atmospheric pressure environments. The variation of corrosion rates is associated with the hydrodynamics at gradual contraction pipe. The presence of high CO2 partial pressure under fluid flowing accelerates rupture of corrosion product scales.

Introduction: Anterior cervical discectomy and fusion (ACDF) is widely accepted as the gold standard surgical procedure for treating cervical radiculopathy and myelopathy. However, there is concern about the low fusion rate in the early period after ACDF surgery using the Zero-P fusion cage. We creatively designed an assembled uncoupled joint fusion device to improve the fusion rate and solve the implantation difficulties. This study aimed to assess the biomechanical performance of the assembled uncovertebral joint fusion cage in single-level ACDF and compare it with the Zero-P device.Methods: A three-dimensional finite element (FE) of a healthy cervical spine (C2−C7) was constructed and validated. In the one-level surgery model, either an assembled uncovertebral joint fusion cage or a zero-profile device was implanted at the C5–C6 segment of the model. A pure moment of 1.0 Nm combined with a follower load of 75 N was imposed at C2 to determine flexion, extension, lateral bending, and axial rotation. The segmental range of motion (ROM), facet contact force (FCF), maximum intradiscal pressure (IDP), and screw−bone stress were determined and compared with those of the zero-profile device.Results: The results showed that the ROMs of the fused levels in both models were nearly zero, while the motions of the unfused segments were unevenly increased. The FCF at adjacent segments in the assembled uncovertebral joint fusion cage group was less than that that of the Zero-P group. The IDP at the adjacent segments and screw–bone stress were slightly higher in the assembled uncovertebral joint fusion cage group than in those of the Zero-P group. Stress on the cage was mainly concentrated on both sides of the wings, reaching 13.4–20.4 Mpa in the assembled uncovertebral joint fusion cage group.Conclusion: The assembled uncovertebral joint fusion cage provided strong immobilization, similar to the Zero-P device. When compared with the Zero-P group, the assembled uncovertebral joint fusion cage achieved similar resultant values regarding FCF, IDP, and screw–bone stress. Moreover, the assembled uncovertebral joint fusion cage effectively achieved early bone formation and fusion, probably due to proper stress distributions in the wings of both sides.

Abstract Background Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. Methods Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. Results Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. Conclusion The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

Tumor metastasis is a common event in patients with gastric cancer (GC) who previously underwent curative gastrectomy. It is meaningful to employ high-volume clinical data for predicting the survival of metastatic GC patients. We aim to establish an improved machine learning (ML) classifier for predicting if a patient with metastatic GC would die within 12 months. Eligible patients were enrolled from a Chinese GC cohort, and the complete detailed information from medical records was extracted to generate a high-dimensional dataset. Appropriate feature engineering and feature filter were conducted before modeling with eight algorithms. A 10-fold cross validation (CV) nested in a holdout CV (8:2) was employed for hyperparameter tuning and model evaluation. Model selection was based on the area under the receiver operating characteristic (AUROC) curve, recall, and precision. The selected model was globally explained using interpretable surrogate models. Of the total 399 cases (median survival of 8.2 months), 242 patients survived less than 12 months. The linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) model had the highest AUROC (0.78 ± 0.021), recall (0.93 ± 0.031), and precision (0.80 ± 0.026), respectively. The LDA model created a new function that generally separated the two classes. The predicted probability of the SVM model was interpreted using a linear regression model visualized by a nomogram. The predicted class of the RF model was explained using a decision tree model. In summary, analyzing high-volume medical data by ML is helpful to produce an improved model for predicting the survival in patients with metastatic GC. The algorithm should be carefully selected in different practical scenarios.

In recent years, cervical spondylosis has become one of the most common chronic diseases and has received much attention from the public. Magnetic resonance imaging (MRI) is the most widely used imaging modality for the diagnosis of degenerative cervical spondylosis. The manual identification and segmentation of the cervical spine on MRI makes it a laborious, time-consuming, and error-prone process. In this work, we collected a new dataset of 300 patients with a total of 600 cervical spine images in the MRI T2-weighted (T2W) modality for the first time, which included the cervical spine, intervertebral discs, spinal cord, and spinal canal information. A new instance segmentation approach called SeUneter was proposed for cervical spine segmentation. SeUneter expanded the depth of the network structure based on the original U-Net and added a channel attention module to the double convolution of the feature extraction. SeUneter could enhance the semantic information of the segmentation and weaken the characteristic information of non-segmentation to the screen for important feature channels in double convolution. In the meantime, to alleviate the over-fitting of the model under insufficient samples, the Cutout was used to crop the pixel information in the original image at random positions of a fixed size, and the number of training samples in the original data was increased. Prior knowledge of the data was used to optimize the segmentation results by a post-process to improve the segmentation performance. The mean of Intersection Over Union (mIOU) was calculated for the different categories, while the mean of the Dice similarity coefficient (mDSC) and mIOU were calculated to compare the segmentation results of different deep learning models for all categories. Compared with multiple models under the same experimental settings, our proposed SeUneter’s performance was superior to U-Net, AttU-Net, UNet++, DeepLab-v3+, TransUNet, and Swin-Unet on the spinal cord with mIOU of 86.34% and the spinal canal with mIOU of 73.44%. The SeUneter matched or exceeded the performance of the aforementioned segmentation models when segmenting vertebral bodies or intervertebral discs. Among all models, SeUneter achieved the highest mIOU and mDSC of 82.73% and 90.66%, respectively, for the whole cervical spine.

Abstract Background To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. Methods Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. Results Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). Conclusions For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. Trial registration This project has been registered in the Chinese Clinical Trial Registry ( ChiCTR1800019978 ).

ObjectiveTo conduct a high-level meta-analysis of the RCTs to evaluate perioperative steroids use in the management of fusion rate, dysphagia, and VAS following anterior cervical spine surgery for up to 1 year.MethodsWe searched the database PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, Ovid, and ClinicalTrials.gov without time restriction to identify RCTs that evaluate the effectiveness of perioperative steroids after anterior cervical spine surgery. A subgroup analysis was undertaken to investigate the effects of intravenous and local steroids. This study was registered in the PROSPERO database prior to initiation (CRD42022313444).ResultsA total of 14 RCTs were eligible for final inclusion. This meta-analysis showed that steroids could achieve lower dysphagia rate (p

BackgroundMore than 70 percent of the world's population is tortured with neck pain more than once in their vast life, of which 50–85% recur within 1–5 years of the initial episode. With medical resources affected by the epidemic, more and more people seek health-related knowledge via YouTube. This article aims to assess the quality and reliability of the medical information shared on YouTube regarding neck pain.MethodsWe searched on YouTube using the keyword “neck pain” to include the top 50 videos by relevance, then divided them into five and seven categories based on their content and source. Each video was quantitatively assessed using the Journal of American Medical Association (JAMA), DISCERN, Global Quality Score (GQS), Neck Pain-Specific Score (NPSS), and video power index (VPI). Spearman correlation analysis was used to evaluate the correlation between JAMA, GQS, DISCERN, NPSS and VPI. A multiple linear regression analysis was applied to identify video features affecting JAMA, GQS, DISCERN, and NPSS.ResultsThe videos had a mean JAMA score of 2.56 (SD = 0.43), DISCERN of 2.55 (SD = 0.44), GQS of 2.86 (SD = 0.72), and NPSS of 2.90 (SD = 2.23). Classification by video upload source, non-physician videos had the greatest share at 38%, and sorted by video content, exercise training comprised 40% of the videos. Significant differences between the uploading sources were observed for VPI (P = 0.012), JAMA (P < 0.001), DISCERN (P < 0.001), GQS (P = 0.001), and NPSS (P = 0.007). Spearman correlation analysis showed that JAMA, DISCERN, GQS, and NPSS significantly correlated with each other (JAMA vs. DISCERN, p < 0.001, JAMA vs. GQS, p < 0.001, JAMA vs. NPSS, p < 0.001, DISCERN vs. GQS, p < 0.001, DISCERN vs. NPSS, p < 0.001, GQS vs. NPSS, p < 0.001). Multiple linear regression analysis suggested that a higher JAMA score, DISCERN, or GQS score were closely related to a higher probability of an academic, physician, non-physician or medical upload source (P < 0.005), and a higher NPSS score was associated with a higher probability of an academic source (P = 0.001) than of an individual upload source.ConclusionsYouTube videos pertaining to neck pain contain low quality, low reliability, and incomplete information. Patients may be put at risk for health complications due to inaccurate, and incomplete information, particularly during the COVID-19 crisis. Academic groups should be committed to high-quality video production and promotion to YouTube users.

Abstract Objective To preliminarily evaluate the safety and efficacy of the uncovertebral joint fusion cage in a goat model of cervical spine interbody fusion. Methods Twenty-four healthy adult goats were randomly assigned to one of the two following groups: Group A, goats were implanted with an uncovertebral joint fusion cage combined with a local autograft and Group B, goats were implanted with a non-profile cage filled with a local autograft. The goats were prospectively evaluated for 24 weeks and then were sacrificed for evaluation. X-rays, CT and micro-CT scanning, and undecalcified bone histological analysis were used for the evaluation of fusion. Results 75.0% (9/12) of the goats in Group A were evaluated as having fusion at 12 weeks, compared to 41.7% (5/12) in Group B. 83.3% (10/12) of the goats in Group A were evaluated as having fusion at 24 weeks compared to 58.3% (7/12) in Group B. The fusion grading scores in Group A were significantly higher than that in Group B both at 12 weeks and 24 weeks (P

Background: The traditional titanium mesh cage (TTMC) has become common as a classical instrument for Anterior Cervical Corpectomy and Fusion (ACCF), but a series of complications such as cage subsidence, adjacent segment degeneration (ASD), and implant-related complications by using the TTMC have often been reported in the previous literature. The aim of this study was to assess whether a novel anatomic titanium mesh cage (NTMC) could improve the biomechanical condition after surgery.Methods: The NTMC model consists of two spacers located on both sides of the TTMC which match the anatomic structure between the endplates by measuring patient preoperative cervical computed tomography (CT) data. The ranges of motion (ROMs) of the surgical segments and the stress peaks in the C6 superior endplates, titanium mesh cage (TMC), screw–bone interface, anterior titanium plate, and adjacent intervertebral disc were compared.Results: Compared with the TTMC, the NTMC reduced the surgical segmental ROMs by 89.4% postoperatively. The C6 superior endplate stress peaks were higher in the TTMC (4.473–23.890 MPa), followed by the NTMC (1.923–5.035 MPa). The stress peaks on the TMC were higher in the TTMC (47.896–349.525 MPa), and the stress peaks on the TMC were lower in the NTMC (17.907–92.799 MPa). TTMC induced higher stress peaks in the screw–bone interface (40.0–153.2 MPa), followed by the NTMC (14.8–67.8 MPa). About the stress peaks on the anterior titanium plate, the stress of TTMC is from 16.499 to 58.432 MPa, and that of the NTMC is from 12.456 to 34.607 MPa. Moreover, the TTMC induced higher stress peaks in the C3/4 and C6/7 intervertebral disc (0.201–6.691 MPa and 0.248–4.735 MPa, respectively), followed by the NTMC (0.227–3.690 MPa and 0.174–3.521 MPa, respectively).Conclusion: First, the application of the NTMC can effectively decrease the risks of TMC subsidence after surgery. Second, in the NTMC, the stresses at the anterior screw-plate, bone–screw, and TMC interface are much less than in the TTMC, which decreased the risks of instrument-related complications after surgery. Finally, increases in IDP at adjacent levels are associated with the internal stresses of adjacent discs which may lead to ASD; therefore, the NTMC can effectively decrease the risks of ASD.

Abstract Background Ovarian squamous cell carcinoma (SCC) is a rare cancer with possible poor survival, however no direct evidence supports this viewpoint and the independent prognostic factors are controversial. Patients with ovarian SCC and serous carcinoma (SC) who were diagnosed between 2004 and 2016 were selected using the recent released SEER database. Propensity score matching was used to balance the characteristics of the two groups. The difference of survival between patients with ovarian SCC and SC was explored using Kaplan-Meier method. Cox regression analyses were performed to further identify the independent prognostic factors among patients with ovarian SCC. Results Of 15,286 patients (15,106 SC cases and 180 SCC cases), 304 were identified in the matched cohort (200 SC cases and 104 SCC cases). The overall survival and cause-specific survival for patients with SCC were significantly poorer (P log-rank

Abstract. Background:. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear. Methods:. An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting. Results:. The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone. Conclusions:. PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a widely accepted surgical procedure in the treatment of cervical radiculopathy and myelopathy. A solid interbody fusion is of critical significance in achieving satisfactory outcomes after ACDF. However, the current radiographic techniques to determine the degree of fusion are inaccurate and radiative. Several animal experiments suggested that the mechanical load on the spinal instrumentation could reflect the fusion process and evaluated the stability of implant. This study aims to investigate the biomechanical changes during the fusion process and explore the feasibility of reflecting the fusion status after ACDF through the load changes borne by the interbody fusion cage.Methods: The computed tomography (CT) scans preoperatively, immediately after surgery, at 3 months, and 6 months follow-up of patients who underwent ACDF at C5/6 were used to construct the C2–C7 finite element (FE) models representing different courses of fusion stages. A 75-N follower load with 1.0-Nm moments was applied to the top of C2 vertebra in the models to simulate flexion, extension, lateral bending, and axial rotation with the C7 vertebra fixed. The Von Mises stress at the surfaces of instrumentation and the adjacent intervertebral disc and force at the facet joints were analyzed.Results: The facet contact force at C5/6 suggested a significantly stepwise reduction as the fusion proceeded while the intradiscal pressure and facet contact force of adjacent levels changed slightly. The stress on the surfaces of titanium plate and screws significantly decreased at 3 and 6 months follow-up. A markedly changed stress distribution in extension among three models was noted in different fusion stages. After solid fusion is achieved, the stress was more uniformly distributed interbody fusion in all loading conditions.Conclusions: Through a follow-up study of 6 months, the stress on the surfaces of cervical instrumentation remarkably decreased in all loading conditions. After solid intervertebral fusion formed, the stress distributions on the surfaces of interbody cage and screws were more uniform. The stress distribution in extension altered significantly in different fusion status. Future studies are needed to develop the interbody fusion device with wireless sensors to achieve longitudinal real-time monitoring of the stress distribution during the course of fusion.

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43]; P = 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18]; P = 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35]; P = 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

Abstract Background Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. Methods The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004–2011, while the validation dataset included 407 patients diagnosed in 2012–2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. Results Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693–0.710) and 0.699 (95% CI: 0.682–0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620–0.639) and 0.607 (95% CI: 0.588–0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score > 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. Conclusions Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.

Conventional zero-shot learning aims to train a classifier on a training set (seen classes) to recognize instances of novel classes (unseen classes) by class-level semantic attributes. In generalized zero-shot learning (GZSL), the classifier needs to recognize both seen and unseen classes, which is a problem of extreme data imbalance. To solve this problem, feature generative methods have been proposed to make up for the lack of unseen classes. Current generative methods use class semantic attributes as the cues for synthetic visual features, which can be considered mapping of the semantic attribute to visual features. However, this mapping cannot effectively transfer knowledge learned from seen classes to unseen classes because the information in the semantic attributes and the information in visual features are asymmetric: semantic attributes contain key category description information, while visual features consist of visual information that cannot be represented by semantics. To this end, we propose a residual-prototype-generating network (RPGN) for GZSL that extracts the residual visual features from original visual features by an encoder–decoder and synthesizes the prototype visual features associated with semantic attributes by a disentangle regressor. Experimental results show that the proposed method achieves competitive results on four GZSL benchmark datasets with significant gains.

Meningiomas, the most common brain tumor, inevitably require surgical treatment. However, the efficacy of prophylactic antiepileptic drugs (AEDs), in reducing the frequency of new-onset seizures during the perioperative period remains controversial. To further clarify if prophylactic antiepileptic drug treatment for patients with meningioma had value, we reviewed the medical records of 186 supratentorial meningioma patients who were operated at our hospital between 2016 and 2018. SPSS 24.0 software was used for statistical analysis. The results of univariate analysis showed that factors including age, sex, the course of the disease (years), maximum cross-sectional area of the tumor, location of the tumor, multiple or single tumors, adjacent to the cortex, peritumoral brain edema, World Health Organization classification, and peritumoral adhesion were not associated with perioperative seizures (P >0.05). Furthermore, the results of multivariate analysis revealed hydrocephalus (OR 4.87 P = 0.05) and non-skull base location (OR 1.88 P = 0.04) were significant risk factors for perioperative in-hospital seizures. Prophylactic valproic acid treatment did not contribute to the alleviation of perioperative seizures (OR 1.76 P = 0.04). However, Multivariate logistic regression analyses excluding the patients with seizures before operation confirmed prophylactic valproic acid treatment did not reduce the frequency of seizures during the perioperative period (OR 1.84 P = 0.04). Taken together, the data suggest that prophylactic valproic acid treatment for patients with supratentorial meningioma does not reduce the rate of perioperative seizures.

Abstract Background Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, causing a major risk of liver disease and hepatocellular carcinoma (HCC). Many mouse models have been tried to establish HBV infection through injection with various HBV-containing plasmids. However, it is not well understood that different plasmids, all of which contain the similar HBV genome, even the same plasmids with different dose, results in opposite immune responses toward HBV. Methods In this study, we investigated the role of HBV-containing plasmid backbones and the HBcAg in determining the HBV persistence. C57BL/6 mice were injected hydrodynamically with 6 μg or 20 μg of WT pAAV/HBV1.2 plasmid, e/core-null pAAV/HBV1.2 plasmid, or none-HBV genome pAAV/control plasmid. Serum levels of HBV-related markers were measured by quantitative immunoradiometric assay (IRMA). Liver HBcAg expression was detected by immunohistochemical staining. The mRNA levels of cytokines and Th1-related immune factors were quantified by qRT-PCR. Results All mice injected with 6 μg of the pAAV/HBV1.2 plasmid shows HBsAg positive at week 6 after hydrodynamic injection (AHI) as previously investigated. However, the mice injected with 20 μg pAAV/HBV1.2 or 6μgpAAV/HBV1.2 plus 14μgpAAV/control plasmid results in HBV clearance within 4 weeks AHI, indicating the anti-HBV activity is induced by 20 μg plasmid DNA, but not by the inserted viral genome. This anti-HBV activity is independent of HBcAg and Toll like receptor (TLR) signaling pathway, since the lack of HBcAg in pAAV/HBV1.2 plasmid or stimulation with TLRs agonists does not influence the kinetics of serum HBsAg in mice. The mRNA levels of t-bet and cxcr3 were dramatically up-regulated in the liver of the mice injected with 20 μg plasmid DNA. Conclusion Our studies demonstrate that plasmid backbones are responsible for modulating immune responses to determine HBV persistence or clearance in our HBV mouse model by hydrodynamic injection of HBV-containing plasmid, and Th1 cells play key roles on HBV clearance.

IIncarvillea arguta belongs to the family Bignoniaceae, is an economically and medicinally important plant. The complete chloroplast genome of I. arguta is 159,135 bp in size, including a large single copy (LSC) region of 87.192 bp, a small single copy (SSC) region of 19,023 bp and a pair of inverted repeats (IRs) of 26,460 bp. The genome contains 108 genes, including 72 protein-coding genes, 32 tRNA genes, and 4 rRNA genes. The GC content in chloroplast genome, LSC region, SSC region, and IR region were 39.5%, 37.9%, 34.7%, and 43.7%, respectively. The evolutionary analysis suggested that I. arguta is related to Tecomaria capensis.

Based on structures and dependencies of the image codestreams, a scalable stream-level authentication ap-proach was proposed to resist packet loss. To construct the authentication algorithm by hash chaining and error-correction coding, the proposed approach can realize optimizing bit-rate allocations and unequal authentication protection. Firstly, the compressed streams of the original image are analyzed to obtain hierarchical structures and coding dependencies. Secondly, in accordance with the differentiation-importance of codestreams to the reconstructed image, sub-important packet is linked to more important packets via hash chains. Finally, these hash values of decoding-independent packets and the digital signature of the whole bitstream are encoded with an error-correction coding algorithm. The proposed scheme has a very low authentication overhead because it signs on the whole image once. Experimental results show that the authenticated image of the proposed scheme has high reconstructed quality than the other three stream-level authenti-cation schemes.