The global burden and risk factors of cardiovascular diseases in adolescent and young adults, 1990-2019.

BACKGROUND: To provide details of the burden and the trend of the cardiovascular disease (CVD) and its risk factors in adolescent and young adults. METHODS: Age-standardized rates (ASRs) of incidence, mortality and Disability-Adjusted Life Years (DALYs) were used to describe the burden of CVD in adolescents and young adults. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by Population Attributable Fractions (PAFs). RESULTS: In 2019, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) of CVD were 129.85 per 100 000 (95% Confidence interval (CI): 102.60, 160.31), 15.12 per 100 000 (95% CI: 13.89, 16.48) and 990.64 per 100 000 (95% CI: 911.06, 1076.46). The highest ASRs were seen in low sociodemographic index (SDI) and low-middle SDI regions. The burden was heavier in male and individuals aged 35-39. From 1990 to 2019, 72 (35.29%) countries showed an increasing trend of ASIR and more than 80% countries showed a downward trend in ASMR and ASDR. Rheumatic heart disease had the highest ASIR and Ischemic Heart Disease was the highest in both ASMR and ASDR. The main attributable risk factor for death and DALYs were high systolic blood pressure, high body-mass index and high LDL cholesterol. CONCLUSIONS: The burden of CVD in adolescent and young adults is a significant global health challenge. It is crucial to take into account the disparities in SDI levels among countries, gender and age characteristics of the population, primary types of CVD, and the attributable risk factors when formulating and implementing prevention strategies.

Carbon Quantum Dots/Cu2O Photocatalyst for Room Temperature Selective Oxidation of Benzyl Alcohol.

The luminescence properties and excellent carrier transfer ability of carbon quantum dots (CQDs) have attracted much attention in the field of photocatalysis. In this work, we loaded the CQDs on the surface of Cu2O to enhance the visible-light property of Cu2O. Furthermore, the composite was used for selective oxidation of benzyl alcohol to benzaldehyde. The composite catalyst achieved high selectivity (90%) for benzaldehyde at room temperature, leveraging its visible-light-induced electron transfer properties and its photocatalytic activity for hydrogen peroxide decomposition. ·OH was shown to be the main reactive oxygen species in the selective oxidation reaction of benzyl alcohol. The formation of heterostructures of CQDs/Cu2O promoted charge carrier separation and provided a fast channel for photoinduced electron transfer. This novel material exhibited enhanced levels of activity and stability for selective oxidation of benzyl alcohol. Potential applications of carbon quantum dot composites in conventional alcohol oxidation reactions are shown.

Global Burden of Ischemic Heart Disease in Adolescents and Young Adults, 1990-2019.

INTRODUCTION: Few studies have evaluated the global burden of ischemic heart disease (IHD) in adolescents and young adults (AYAs). METHODS: Age-standardized rates (ASRs) of incidence (ASIR), mortality (ASMR) and Disability-Adjusted Life Years (DALYs) (ASDR) were used to describe the burden of IHD in AYAs. Estimated Annual Percentage Changes (EAPCs) of ASRs were used to describe the trend from 1990 to 2019. Risk factors were calculated by population attributable fractions (PAFs). Analyses were conducted in 2023. RESULTS: In 2019, the ASIR, ASMR, and ASDR of IHD in AYAs were 26.81 (95% uncertainty interval [UI]: 20.36-34.54) per 100,000, 7.15 (95% UI: 6.56-7.87) per 100,000 and 409.51 (95% UI: 376.57-449.59) per 100,000. The ASIR and ASMR were higher among men than among women. From 1990 to 2019, the ASIR increased (EAPC=0.18%, 95% CI 0.14%-0.22%), while the ASMR (EAPC=-0.39%, -0.50% to -0.27%) and ASDR (EAPC=-0.40%, -0.52% to -0.29%) decreased. The largest increase in ASIR was observed in countries with a middle sociodemographic index (SDI) (EAPC=0.56%, 0.51%-0.60%). Globally, the proportional contribution of risk factors for DALY varied across regions, with the highest proportions of high low-density lipoprotein cholesterol in high SDI regions (PAF=74.26%) and high-middle (PAF=71.30%) and the highest proportions of air pollution in low (PAF=41.79%) and low-middle SDI regions (PAF=40.90%). CONCLUSIONS: The burden of IHD in AYAs remains high globally, and varies by age, sex, (male/female), region, and country. Targeted measures are needed to address the rising burden of IHD in AYAs, focusing on prevention, early diagnosis, and reduction in disparities.

Boosting uniform nucleation and suppressing hydrogen evolution with an in-situ formed zinc hyaluronate protective film on zinc anodes.

Developing long-cycle stable Zn-ion batteries encounters significant challenges associated with Zn anodes. To address these issues, we propose an interface engineering strategy using an artificial protective layer called zinc hyaluronate (ZH) on the Zn anode surface. The ZH film acts as a barrier, preventing direct contact between Zn anode and electrolyte, reducing hydrogen evolution and corrosion. Its carboxyl and hydroxyl groups create uniform and plentiful nucleophilic sites for Zn2+ ions, promoting uniform Zn deposition and suppressing dendrite growth. Remarkably, a Zn//Zn symmetric cell assembled with ZH-decorated Zn foil (Zn@ZH) exhibits outstanding cycle life, lasting 3600 h at a current density of 5 mA cm-2 and a capacity density of 5 mAh cm-2, much better than cells with pristine Zn anode. Even under extremely tough conditions of 10 mA cm-2 and 10 mAh cm-2, the battery life exceeds 1300 h. Furthermore, the Zn@ZH//V2O5 full cell demonstrates superior capacity retention compared to the Zn//V2O5 cell after 1000 cycles at a current density of 10 A g-1. These results highlight the benefits of the artificial protective layer strategy for advanced Zn anodes, providing insights into the underlying mechanism and promoting the development of high-performance aqueous zinc ion batteries.

Spatiotemporal trends in global burden of rheumatic heart disease and associated risk factors from 1990 to 2019.

BACKGROUND: The aim of this study was to estimate the burden of rheumatic heart disease (RHD) and its trends in different countries, regions, genders and age groups globally. METHODS: Data were obtained from the Global Burden of Disease 2019 study. Age-standardized rates (ASRs) and the estimated annual percentage changes (EAPCs) in the ASRs were used to describe the burden of disease and its trends. Pearson's correlation was used to evaluate the correlation between sociodemographic index (SDI) values and the observed trends. RESULTS: In 2019, the ASRs of the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of RHD were 37.39/105 (95%UI, 28.59/105 to 46.74/105), 513.68/105 (95%UI, 405.01/105 to 636.25/105), 3.85/105 (95%UI, 4.29/105 to 3.29/105) and 132.88/105 (95%UI, 115.02/105 to 150.34/105), respectively. From 1990 to 2019, the incidence and prevalence of RHD showed upward trends and the mortality and DALYs showed downward trends. Countries or regions in Africa, South America and South Asia had a greater burden of RHD. The burden of RHD was greater in women, where as men showed more obvious increasing trends in the incidence and prevalence. The incidence of RHD was highest in adolescents, and the prevalence was highest in young and middle-aged. The mortality and DALYs rate associated with RHD increased with age. The EAPCs in the ASRs were negatively correlated with the SDI value. CONCLUSION: Although the ASRs of mortality and DALYs attributable to RHD are decreasing globally, RHD remains an important public health problem that needs to be addressed urgently, especially in certain low- and middle-income countries and regions.

The relationship between tumor infiltrating immune cells and the prognosis of patients with lung adenocarcinoma.

Background: To depict the immune infiltration characteristics of tumor cells in patients with lung adenocarcinoma (LUAD) and evaluate the predictive value and significance of tumor immune cells on the prognosis of LUAD patients. Methods: The clinical characteristics and transcriptome of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the immune cell abundance in LUAD tissue was evaluated using the CIBERSORT algorithm. We created a simplified immune cell-based Cox regression model according to the survival status of patients and clarified the correlation between the survival status of patients and seven types of immune cells. An immune cell-based risk prediction model was created by Cox proportional hazards regression. Subsequently, the gene expression profile of LUAD patients was obtained from the Gene Expression Omnibus (GEO) database to validate the tumor immune infiltration and patient prognosis prediction model attained using the CIBERSORT algorithm. Results: The abundance of 22 tumor-infiltrating immune cells in these patients was detected using the CIBERSORT algorithm. According to Pearson correlation analysis, the immune cells appeared to be closely related to each other. The immune cell composition was remarkably different between the LUAD tumor tissue and paracancerous tissue. The simplified COX model showed that seven kinds of immune cells have predictive value for the prognosis and survival status of LUAD. The receiver operating characteristic curve (ROC) curve confirmed that the prediction model performed well for 1-, 3-, and 5-year survival status. The calibration curve suggested that the prediction model was consistent with the clinical results. Correlation analysis revealed that the clinical features were significantly related to immune cell infiltration. A total of 246 LUAD specimens were from the GEO database, and the risk score model suggested that high risk scores were indicative of a poor prognosis. Finally, enzyme-linked immunosorbent assay (ELISA) revealed that the expressions of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), IL-6, and interferon-γ (IFN-γ) in tumor tissues were remarkably higher compared with those in adjacent tissues. Conclusions: There is a close correlation between the tumor-infiltrating immune cells and the prognosis and clinical characteristics of LUAD patients. The risk score model based on TCGA and GEO designed in this study can be applied in clinical practice.

Global, Regional, and National Burdens of Ischemic Heart Disease Attributable to Smoking From 1990 to 2019.

Background This study was conducted to estimate the distribution of and changes in the global disease burden of ischemic heart disease attributable to smoking between 1990 and 2019. Methods and Results Data used in this study come from the GBD 2019 (Global Burden of Disease Study 2019). Age-standardized rates and estimated annual percentage change of age-standardized rates were used to describe this burden and its changing trend. Pearson's correlation coefficient was used to evaluate the correlation between the sociodemographic index and changing trend. From 1990 to 2019, the burden of ischemic heart disease attributable to smoking has shown a downward trend globally; estimated annual percentage changes of age-standardized mortality rates and age-standardized disability-adjusted life-years rates were -2.012 (95% CI, -2.068 to -1.956) and -1.907 (95% CI, -1.975 to -1.838). Nineteen countries experienced an increase in disease burden, and the changes in 17 countries were not statistically significant. In addition, this burden was higher in men and older age groups. Estimated annual percentage change of the age-standardized rates of this burden were negatively correlated with the sociodemographic index. Conclusions Although the burden of ischemic heart disease attributable to smoking has decreased in >80% of countries or regions in the past 30 years, it has remained a significant issue in low- and middle-income countries, particularly among men and elderly populations. Therefore, active tobacco control measures, focusing on key populations, are required to reduce the associated burden of ischemic heart disease, especially in those countries or regions with increasing prevalence and disease burden.

The Global, Regional, and National Burdens of Cervical Cancer Attributable to Smoking From 1990 to 2019: Population-Based Study.

BACKGROUND: Cervical cancer is the fourth most common cause of cancer death in women worldwide. Smoking is one of the risk factors for cervical cancer. Understanding the global distribution of the disease burden of cervical cancer attributable to smoking and related changes is of clear significance for the prevention and control of cervical cancer in key populations and for tobacco control. As far as we know, research on the burden of cervical cancer attributable to smoking is lacking. OBJECTIVE: We estimated the disease burden and mortality of cervical cancer attributable to smoking and related trends over time at the global, regional, and national levels. METHODS: Data were obtained from the Global Burden of Disease study website. Age-standardized rates were used to facilitate comparisons of mortality and disability-adjusted life years (DALYs) at different levels. The estimated annual percentage change (EAPC) was used to assess trends in the age-standardized mortality rate (ASMR) and the age-standardized DALY rate (ASDR). A Pearson correlation analysis was used to evaluate correlations between the sociodemographic index and the age-standardized rates. RESULTS: In 2019, there were 30,136.65 (95% uncertainty interval [UI]: 14,945.09-49,639.87) cervical cancer-related deaths and 893,735.25 (95% UI 469,201.51-1,440,050.85) cervical cancer-related DALYs attributable to smoking. From 1990 to 2019, the global burden of cervical cancer attributable to smoking showed a decreasing trend around the world; the EAPCs for ASMR and ASDR were -2.11 (95% CI -2.16 to -2.06) and -2.22 (95% CI -2.26 to -2.18), respectively. In terms of age characteristics, in 2019, an upward trend was observed for age in the mortality of cervical cancer attributable to smoking. Analysis of the trend in DALYs with age revealed an initially increasing and then decreasing trend. From 1990 to 2019, the burden of disease in different age groups showed a downward trend. Among 204 countries, 180 countries showed downward trends, 10 countries showed upward trends, and the burden was stable in 14 countries. The Pearson correlation analysis revealed a significant negative correlation between sociodemographic index and the age-standardized rates of cervical cancer attributable to smoking (ρ=-0.228, P<.001 for ASMR and ρ=-0.223, P<.001 for ASDR). CONCLUSIONS: An increase over time in the absolute number of cervical cancer deaths and DALYs attributable to smoking and a decrease over time in the ASMR and ASDR for cervical cancer attributable to smoking were observed in the overall population, and differences in these variables were also observed between countries and regions. More attention should be paid to cervical cancer prevention and screening in women who smoke, especially in low- and middle-income countries.

Marine Biomass-Supported Nano Zero-Valent Iron for Cr(VI) Removal: A Response Surface Methodology Study.

Heavy metal ions such as Cr(VI) pose great hazards to the environment, which requests materials and methods for decontamination. Nano zero-valent iron (nZVI) has emerged as a promising candidate for Cr(VI) removal. Herein, harnessing the merits of marine biomass, a heterogeneous water treatment system for the decontamination of Cr(VI) is developed based on the in situ immobilization of nZVI on the seashell powder (SP)-derived porous support. A response surface methodology (RSM) study involving three independent factors is designed and conducted to direct material synthesis and reaction design for products with optimal performances. Under optimal synthetic conditions, the nZVI-loaded seashell powder (SP@nZVI), which is characterized in detail by scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR), results in a 79% increase in the removal efficiency of Cr(VI) compared to free nZVI. Mechanism studies show that the removal of Cr(VI) by SP@nZVI conforms to the Langmuir adsorption model with a quasi-second order kinetic equation, in which redox reactions between nZVI and Cr(VI) occurred at the SP surface. The results of this work are expected to benefit the reuse of bioresource waste in developing environmental remediation materials.

Ursolic acid ameliorates adipose tissue insulin resistance in aged rats via activating the Akt-glucose transporter 4 signaling pathway and inhibiting inflammation.

Ageing often results in insulin resistance (IR) and chronic inflammation, and adipose is one of the tissues in which inflammation and IR occur earliest during this process. The present study investigated the effect and underlying mechanisms of ursolic acid (UA) on adipose IR and inflammation in ageing rats. Specific pathogen-free male Sprague-Dawley rats were randomly divided into 4 groups: i) Young normal (young); ii) untreated ageing (aged); and groups supplemented with UA either iii) low-UA 10 mg/kg (UA-L) or iv) high-50 mg/kg (UA-H). Animals in the UA-treated groups received 10 or 50 mg/kg UA (suspended in 5% Gum Arabic solution). The rats in the corresponding aged group and young groups received vehicle (5% Gum Arabic) alone. All rats were intragastrically treated once daily by oral gavage for 7 weeks. The day before the experiment terminated, overnight fasting blood (~700 µl) was collected and plasma was prepared to measure biochemical indicators; western blotting was performed to analyze the expression of insulin signaling proteins [(insulin receptor substrate 1 (IRS-1), phosphorylated (p)-IRS-1, PI3K, glucose transporter 4 (GLUT4), Akt and p-Akt)] and inflammatory factors (NF-κB, IL-6 and IL-1ß) in the epididymis white adipose tissue (eWAT). The results revealed that treatment with UA-H decreased eWAT weight, the ratio of eWAT weight/body weight, fasted insulin and triglyceride levels, the homeostasis model assessment of insulin resistance and adipose tissue insulin resistance index in ageing rats, indicating the amelioration of systemic and adipose tissue IR, compared with the aged group. Mechanistically, UA-H administration upregulated p-protein kinase B, the ratio of p-Akt to protein kinase B and total and cellular membrane GLUT4 protein levels in eWAT of ageing rats. Conversely, UA inhibited the increase in NF-κB expression and proinflammatory cytokines IL-6 and IL-1ß. However, these alterations were not observed in the rats of the aged group. Taken together, the findings of the present study indicated that UA may ameliorate adipose IR, which is associated with activation of the Akt-GLUT4 signaling pathway and inhibition of inflammation in ageing rats. These data provide a basis for the development of effective and safe drugs or functional substances, such as UA, for the prevention and treatment of metabolic diseases.

Application of Big Data and Artificial Intelligence in COVID-19 Prevention, Diagnosis, Treatment and Management Decisions in China.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread rapidly and affected most of the world since its outbreak in Wuhan, China, which presents a major challenge to the emergency response mechanism for sudden public health events and epidemic prevention and control in all countries. In the face of the severe situation of epidemic prevention and control and the arduous task of social management, the tremendous power of science and technology in prevention and control has emerged. The new generation of information technology, represented by big data and artificial intelligence (AI) technology, has been widely used in the prevention, diagnosis, treatment and management of COVID-19 as an important basic support. Although the technology has developed, there are still challenges with respect to epidemic surveillance, accurate prevention and control, effective diagnosis and treatment, and timely judgement. The prevention and control of sudden infectious diseases usually depend on the control of infection sources, interruption of transmission channels and vaccine development. Big data and AI are effective technologies to identify the source of infection and have an irreplaceable role in distinguishing close contacts and suspicious populations. Advanced computational analysis is beneficial to accelerate the speed of vaccine research and development and to improve the quality of vaccines. AI provides support in automatically processing relevant data from medical images and clinical features, tests and examination findings; predicting disease progression and prognosis; and even recommending treatment plans and strategies. This paper reviews the application of big data and AI in the COVID-19 prevention, diagnosis, treatment and management decisions in China to explain how to apply big data and AI technology to address the common problems in the COVID-19 pandemic. Although the findings regarding the application of big data and AI technologies in sudden public health events lack validation of repeatability and universality, current studies in China have shown that the application of big data and AI is feasible in response to the COVID-19 pandemic. These studies concluded that the application of big data and AI technology can contribute to prevention, diagnosis, treatment and management decision making regarding sudden public health events in the future.

FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients.

A patient's response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.

Pacing Electrocardiogram Detection With Memory-Based Autoencoder and Metric Learning.

Remote ECG diagnosis has been widely used in the clinical ECG workflow. Especially for patients with pacemaker, in the limited information of patient's medical history, doctors need to determine whether the patient is wearing a pacemaker and also diagnose other abnormalities. An automatic detection pacing ECG method can help cardiologists reduce the workload and the rates of misdiagnosis. In this paper, we propose a novel autoencoder framework that can detect the pacing ECG from the remote ECG. First, we design a memory module in the traditional autoencoder. The memory module is to record and query the typical features of the training pacing ECG type. The framework does not directly feed features of the encoder into the decoder but uses the features to retrieve the most relevant items in the memory module. In the training process, the memory items are updated to represent the latent features of the input pacing ECG. In the detection process, the reconstruction data of the decoder is obtained by the fusion features in the memory module. Therefore, the reconstructed data of the decoder tends to be close to the pacing ECG. Meanwhile, we introduce an objective function based on the idea of metric learning. In the context of pacing ECG detection, comparing the error of objective function of the input data and reconstructed data can be used as an indicator of detection. According to the objective function, if the input data does not belong to pacing ECG, the objective function may get a large error. Furthermore, we introduce a new database named the pacing ECG database including 800 patients with a total of 8,000 heartbeats. Experimental results demonstrate that our method achieves an average F1-score of 0.918. To further validate the generalization of the proposed method, we also experiment on a widely used MIT-BIH arrhythmia database.

Shell biomass material supported nano-zero valent iron to remove Pb2+ and Cd2+ in water.

Nanoscale zero-valent iron (NZVI) has a high adsorption capacity for heavy metals, but easily forms aggregates. Herein, preprocessed undulating venus shell (UVS) is used as support material to prevent NZVI from reuniting. The SEM and TEM results show that UVS had a porous layered structure and NZVI particles were evenly distributed on the UVS surface. A large number of adsorption sites on the surface of UVS-NZVI are confirmed by IR and XRD. UVS-NZVI is used for adsorption of Pb2+ and Cd2+ at pH = 6.00 in aqueous solution, and the experimental adsorption capacities are 29.91 and 38.99 mg g-1 at optimal pH, respectively. Thermodynamic studies indicate that the adsorption of ions by UVS-NZVI is more in line with the Langmuir model when Pb2+ or Cd2+ existed alone. For the mixed solution of Pb2+ and Cd2+, only the adsorption of Pb2+ by UVS-NZVI conforms to the Langmuir model. In addition, the maximum adsorption capacities of UVS-NZVI for Pb2+ and Cd2+ are 93.01 and 46.07 mg g-1, respectively. Kinetic studies demonstrate that the determination coefficients (R 2) of the pseudo first-order kinetic model for UVS-NZVI adsorption of Cd2+ and Pb2+ are higher than those of the pseudo second-order kinetic model and Elovich kinetic model. Highly efficient performance for metal removal makes UVS-NZVI show potential application to heavy metal ion adsorption.

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway.

BACKGROUND: Esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. MiR-25-3p was proved to be a biomarker for the diagnosis and treatment of many cancers. MiR-25-3p was found to be high expressed in the blood of EC patients. The aim of the present study was to explore the effect of miR-25-3p and its target gene on EC. METHODS: miR-25-3p expression in the blood of EC patients and EC cells was detected by RT-qPCR. The target of miR-25-3p was identified by bioinformatics and luciferase reporter assay. After transfection, cell viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, wound healing, and transwell assays, respectively. The expressions of PTEN, Bax, Bcl-2, cleaved Caspase-3, p-PI3K, PI3K, p-AKT, and AKT were detected by Western blot. RESULTS: MiR-25-3p was high expressed in the blood of EC patients and EC cells. MiR-25-3p targeted PTEN and inhibited the expression of PTEN. MiR-25-3p mimic increased the viability, migration, invasion and the expressions of Bcl-2, and inhibited the apoptosis and the expression of Bax and cleaved caspase-3 in EC cells. MiR-25-3p mimic also enhanced the expressions of p-PI3K and p-AKT and the ratios of p-PI3K/PI3K and p-AKT/AKT in EC cells. PTEN overexpression not only had an opposite effect of miR-25-3p mimic, but also reversed the effect of miR-25-3p mimic on EC cells. CONCLUSION: MiR-25-3p targeted PTEN to promote the migration and invasion, and inhibit apoptosis of EC cells via the PI3K/AKT pathway, which might provide a new therapeutic target for EC treatment.

Changing Technologies of RNA Sequencing and Their Applications in Clinical Oncology.

RNA sequencing (RNAseq) is one of the most commonly used techniques in life sciences, and has been widely used in cancer research, drug development, and cancer diagnosis and prognosis. Driven by various biological and technical questions, the techniques of RNAseq have progressed rapidly from bulk RNAseq, laser-captured micro-dissected RNAseq, and single-cell RNAseq to digital spatial RNA profiling, spatial transcriptomics, and direct in situ sequencing. These different technologies have their unique strengths, weaknesses, and suitable applications in the field of clinical oncology. To guide cancer researchers to select the most appropriate RNAseq technique for their biological questions, we will discuss each of these technologies, technical features, and clinical applications in cancer. We will help cancer researchers to understand the key differences of these RNAseq technologies and their optimal applications.

Calreticulin acts as an adjuvant to promote dendritic cell maturation and enhances antigen-specific cytotoxic T lymphocyte responses against non-small cell lung cancer cells.

Dendritic cell (DC)-based immunotherapy has promising for treatment of non-small cell lung cancer (NSCLC). Melanoma-associated antigen 3 (MAGE-A3) is a tumor-specific antigen and expressed in approximately 35-40% of NSCLC tissues. Calreticulin (CALR) is a protein chaperone and can enhance DC maturation and antigen presentation. In this study, we evaluated the adjuvant activity of CALR in human DC maturation and their capacity to induce MAGE-A3-specific CD8+ cytotoxic T lymphocyte (CTL) responses to NSCLC in vitro. Infection with recombinant Ad-CALR and/or Ad-MAGE-A3, but not with control Ads, induced CALR and/or MAGE-A3 expression in DCs. Infection with Ad-CALR significantly increased the percentages of CD80+, CD83+, CD86+ and HLA-DR+ DCs and IL-12 secretion, but reduced IL-10 production in DCs. Co-culture of autologous lymphocytes with DC-Ad-CALR or DC-Ad-CM significantly increased the numbers of induced CD8+ CTLs. The percentages of IFNγ-secreting CTLs responding to SK-LU-1 and NCI-H522 NSCLC, but not to non-tumor NL-20 cells in Ad-C-CTL, Ad-M-CTL and Ad-CM-CTL were significantly higher than that of DC-CTL and Ad-null-CTL. Ad-C-CTL, Ad-M-CTL and Ad-CM-CTL, but not control DC-CTL and Ad-null-CTL, induced higher frequency of MAGE-A3+HLA-A2+ NCI-H-522 cell apoptosis, but did not affect the survival of MAGE-A3+HLA-A2- SK-LU-1 and non-tumor NL20 cells in vitro. Treatment with anti-HLA-I antibody, but not with anti-HLA-II, dramatically diminished the cytotoxicity of Ad-CM-CTLs against NCI-H522 cells. Our data indicated that CALR acted as an adjuvant to promote DC maturation, which induced CTL development and enhanced MAGE-A3-specific CTL cytotoxicity against NSCLC.

Efficient induction of anti-tumor immune response in esophageal squamous cell carcinoma via dendritic cells expressing MAGE-A3 and CALR antigens.

Despite advances in the various treatment options for esophageal squamous cell carcinoma (ESCC), its prognosis is still very poor with a 5-year survival rate of only 14-22%. Recently, among the various therapeutic approaches, the focus has shifted to immunotherapy, specifically immunotherapy involving dendritic cells (DCs), which depends on their maturation and antigen presentation to effector immune cells. Recent studies have suggested that melanoma-associated antigen 3 (MAGE-A3) is a potential immunotherapeutic target and also a candidate for the development of an anti-tumor vaccine. Calreticulin (CALR) has been shown to support induction of DC maturation. Therefore, in this study, we overexpressed MAGE-A3 and CALR on DCs and studied their potential to generate anti-tumor immune responses. We observed that adenovirus (Ad)-infected DCs overexpressing CALR and MAGE-A3 showed enhanced expression of CD80, CD83, CD86, and HLA-DR markers. Also, these DCs secreted higher levels of interleukin (IL)-12, which induces the T helper type 1 cell (Th1) response, and a lower level of IL-10, a negative regulator of the Th1 response. Furthermore, CALR/MAGE-A3-infected DCs stimulated CD8(+) cytotoxic T lymphocytes, which in turn secreted higher levels of interferon-γ, which induced cytotoxic effects on ESCC cells expressing MAGE-A3. In conclusion, our results revealed the potential of CALR/MAGE-A3-infected DCs to elicit a MAGE-A3-specific anti-tumor immunogenic response in ESCC. This proof-of-principle study may promote the future design and development of DC-based effective immunotherapy against ESCC.

Novel T-shaped linear-stapled intrathoracic esophagogastric anastomosis for minimally invasive Ivor Lewis esophagectomy.

We report a novel T-shaped linear-stapled intrathoracic esophagogastric anastomosis for minimally invasive Ivor Lewis esophagectomy. A unique feature of this technique is a "gastric pouch" that is preserved proximal to the gastric conduit and which serves as the stapler-firing pathway to protect the gastric conduit. The linear stapler is placed through an auxiliary port in the seventh intercostal space on the right posterior axillary line and fired along the longitudinal axis of the thorax, without being constrained by limited intrathoracic space. This technique, which has been performed in 8 patients, is efficient, reliable, and easy to perform.

Anticancer effects of adenovirus-mediated calreticulin and melanoma-associated antigen 3 expression on non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is highly prevalent and needs novel therapies. Melanoma-associated antigen 3 (MAGE-A3) is a lung cancer antigen and calreticulin (CALR) can modulate immune responses. Our previous study has shown that up-regulated MAGE-A3 and CALR expression inhibits the proliferation and invasion of glioma cells. In this study, we examined the effect of adenovirus (Ad)-mediated MAGE-A3 and/or CALR expression on the proliferation, invasion, and apoptosis of human NSCLC cells and on the vascular tube formation of human endothelial cells as well as on dendritic cell (DC) activation and induced CD8(+) cytotoxic T lymphocyte (CTL) activity in vitro. We found that low levels of CALR and MAGE-A3 were expressed by A549 cells, but only very low CALR was expressed by DC. Up-regulated CALR and MAGE-A3 expression by infection with Ad-CALR/MAGE-A3 significantly inhibited the proliferation and invasion, but promoted the apoptosis of A549 cells. Up-regulated CALR and MAGE-A3 expression significantly inhibited cyclin D1 expression and the AKT, ERK1/2 and NF-κB expression and phosphorylation in A549 cells. Up-regulated CALR expression inhibited the tube formation in human endothelial cells. Up-regulated CALR and MAGE-A3 expression synergistically enhanced classical DC activation by enhancing IL-12, but reducing IL-10 secretion. Furthermore, CTLs induced by up-regulated CALR and MAGE-A3 expressing DCs synergistically triggered A549 cell apoptosis, which was abrogated by treatment with anti-HLA I, but not anti-HLA II antibodies. Moreover, CTLs induced by CALR and MAGE-A3-expressing DCs had a higher frequency of A549-specific IFN-γ-secreting T cells. Our data indicated that up-regulated CALR and MAGE-A3 expression inhibited the carcinogenesis of NSCLC by modulating the AKT, ERK MAPK and NF-κB signaling and enhanced classical DC activation and MAGE-A3-specific CTL cytotoxicity. Therefore, our findings may provide new insights in understanding the role of CALR in modulating antigen-specific T cell immunity and may aid in the design of new therapies for NSCLC.