Huadong Hospital

We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. coli endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.

Intelligent 2D theranostic nanomaterials are successfully designed based on pH-/H2O2-responsive MnO2 nanosheets anchored with upconversion nanoprobes. They react with acidic H2O2 to generate sufficient oxygen for enhancing the synergetic radio/photodynamic therapy efficacy upon NIR light/X-ray irradiation and recover/enhance the upconversion luminescence for monitoring the therapeutic process.

In China, lung cancer is a primary cancer type with high incidence and mortality. Risk factors for lung cancer include tobacco use, family history, radiation exposure, and the presence of chronic lung diseases. Most early-stage non-small cell lung cancer (NSCLC) patients miss the optimal timing for treatment due to the lack of clinical presentations. Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China. The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC, thus prolonging survival in patients with positive drivers. In the exploration of immune escape mechanisms, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China. In the Chinese Society of Clinical Oncology's guidelines for NSCLC, maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy. Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC. In this review, we summarized recent advances in NSCLC in China in terms of epidemiology, biology, molecular pathology, pathogenesis, screening, diagnosis, targeted therapy, and immunotherapy.

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression.

<b>Age significantly determined the clinical features and prognosis of COVID-19. The prognosis was worse in patients older than 60 years, calling for clinicians to pay more attention to patients of this age.</b>https://bit.ly/34DTI05

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2-3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of Journal Articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.

In 2014, the International Endohernia Society (IEHS) published the first international "Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias." Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. METHODS: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. RESULTS: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques-minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. CONCLUSION: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

BACKGROUND: Urinary protein quantification is critical for assessing the severity of chronic kidney disease (CKD). However, the current procedure for determining the severity of CKD is completed through evaluating 24-h urinary protein, which is inconvenient during follow-up. OBJECTIVE: To quickly predict the severity of CKD using more easily available demographic and blood biochemical features during follow-up, we developed and compared several predictive models using statistical, machine learning and neural network approaches. METHODS: The clinical and blood biochemical results from 551 patients with proteinuria were collected. Thirteen blood-derived tests and 5 demographic features were used as non-urinary clinical variables to predict the 24-h urinary protein outcome response. Nine predictive models were established and compared, including logistic regression, Elastic Net, lasso regression, ridge regression, support vector machine, random forest, XGBoost, neural network and k-nearest neighbor. The AU-ROC, sensitivity (recall), specificity, accuracy, log-loss and precision of each of the models were evaluated. The effect sizes of each variable were analysed and ranked. RESULTS: The linear models including Elastic Net, lasso regression, ridge regression and logistic regression showed the highest overall predictive power, with an average AUC and a precision above 0.87 and 0.8, respectively. Logistic regression ranked first, reaching an AUC of 0.873, with a sensitivity and specificity of 0.83 and 0.82, respectively. The model with the highest sensitivity was Elastic Net (0.85), while XGBoost showed the highest specificity (0.83). In the effect size analyses, we identified that ALB, Scr, TG, LDL and EGFR had important impacts on the predictability of the models, while other predictors such as CRP, HDL and SNA were less important. CONCLUSIONS: Blood-derived tests could be applied as non-urinary predictors during outpatient follow-up. Features in routine blood tests, including ALB, Scr, TG, LDL and EGFR levels, showed predictive ability for CKD severity. The developed online tool can facilitate the prediction of proteinuria progress during follow-up in clinical practice.

OBJECTIVE: To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: Exercise therapy appears to be effective at decreasing pain and improving function for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP. METHODS: Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies. RESULTS: From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain [mean difference (-1.29); 95% confidence interval (-2.47, -0.11); P = 0.003] and disability [mean difference (-7.14); 95% confidence interval (-11.64, -2.65); P = 0.002] at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months [mean difference (-0.50); 95% confidence interval (-1.36, 0.36); P = 0.26] and 12 months [mean difference (-0.32); 95% confidence interval (-0.87, 0.23); P = 0.25]. CONCLUSIONS: Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise. SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept all over the world, posing a great pressure on critical care resources due to large number of patients needing critical care. Statements from front-line experts in the field of intensive care are urgently needed. METHODS: Sixteen front-line experts in China fighting against the COVID-19 epidemic in Wuhan were organized to develop an expert statement after 5 rounds of expert seminars and discussions to provide trustworthy recommendation on the management of critically ill COVID-19 patients. Each expert was assigned tasks within their field of expertise to provide draft statements and rationale. Parts of the expert statement are based on epidemiological and clinical evidence, without available scientific evidences. RESULTS: A comprehensive document with 46 statements are presented, including protection of medical personnel, etiological treatment, diagnosis and treatment of tissue and organ functional impairment, psychological interventions, immunity therapy, nutritional support, and transportation of critically ill COVID-19 patients. Among them, 5 recommendations were strong (Grade 1), 21 were weak (Grade 2), and 20 were experts' opinions. A strong agreement from voting participants was obtained for all recommendations. CONCLUSION: There are still no targeted therapies for COVID-19 patients. Dynamic monitoring and supportive treatment for the restoration of tissue vascularization and organ function are particularly important.

BACKGROUND: Coffee consumption has been shown to be associated with cancer of various sites in epidemiological studies. However, there is no comprehensive overview of the substantial body of epidemiologic evidence. METHODS: We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Prospective cohort studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of various cancers with respect to frequency of coffee intake. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with 1 cup/day increment of coffee consumption. RESULTS: 59 studies, consisting of 40 independent cohorts, met the inclusion criteria. Compared with individuals who did not or seldom drink coffee per day, the pooled RR of cancer was 0.87 (95% CI, 0.82-0.92) for regular coffee drinkers, 0.89 (0.84-0.93) for low to moderate coffee drinkers, and 0.82 (0.74-0.89) for high drinkers. Overall, an increase in consumption of 1 cup of coffee per day was associated with a 3% reduced risk of cancers (RR, 0.97; 95% CI, 0.96-0.98). In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of bladder, breast, buccal and pharyngeal, colorectal, endometrial, esophageal, hepatocellular, leukemic, pancreatic, and prostate cancers. CONCLUSIONS: Findings from this meta-analysis suggest that coffee consumption may reduce the total cancer incidence and it also has an inverse association with some type of cancers.

The functional role of respiratory microbiota has attracted an accumulating attention recently. However, the role of respiratory microbiome in lung carcinogenesis is mostly unknown. Our study aimed to characterize and compare bilateral lower airway microbiome of lung cancer patients with unilateral lobar masses and control subjects. Protected bronchial specimen brushing samples were collected from 24 lung cancer patients with unilateral lobar masses (paired samples from cancerous site and the contralateral noncancerous site) and 18 healthy controls undergoing bronchoscopies and further analyzed by 16S rRNA amplicon sequencing. As results, significant decreases in microbial diversity were observed in patients with lung cancer in comparison to the controls, alpha diversity steadily declined from healthy site to noncancerous to cancerous site. Genus Streptococcus was significantly more abundant in cancer cases than the controls, while Staphylococcus was more abundant in the controls. The area under the curve of genus Streptococcus used to predict lung cancer was 0.693 (sensitivity = 87.5%, specificity = 55.6%). The abundance of genus Streptococcus and Neisseria displayed an increasing trend whereas Staphylococcus and Dialister gradually declined from healthy to noncancerous to cancerous site. Collectively, lung cancer-associated microbiota profile is distinct from that found in healthy controls, and the altered cancer-associated microbiota is not restricted to tumor tissue. The genus Streptococcus was abundant in lung cancer patients and exhibited moderate classification potential. The gradual microbiota profile shift from healthy site to noncancerous to paired cancerous site suggested a change of the microenvironment associated with the development of lung cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common primary malignant tumor which usually progresses to an advanced stage because of late diagnosis. Sorafenib (Sora) is a first line medicine for advanced stage HCC; however, it has been faced with enormous resistance. Simvastatin (Sim) is a cholesterol-lowering drug and has been reported to inhibit tumor growth. The present study aims to determine whether Sora and Sim co-treatment can improve Sora resistance in HCC. METHODS: The HCC cell line LM3 and an established Sora-resistant LM3 cell line (LM3-SR) were used to study the relationship between Sora resistance and aerobic glycolysis. Cell proliferation, apoptosis and glycolysis levels were analyzed by western blotting, flow cytometry analysis and biomedical tests. A xenograft model was also used to examine the effect of Sim in vivo. Detailed mechanistic studies were also undertaken by the use of activators and inhibitors, and lentivirus transfections. RESULTS: Our results demonstrated that the resistance to Sora was associated with enhanced aerobic glycolysis levels. Furthermore, LM3-SR cells were more sensitive to Sim than LM3 cells, suggesting that combined treatment with both Sora and Sim could enhance the sensitivity of LM3-SR cells to Sora. This finding may be due to the suppression of the HIF-1α/PPAR-γ/PKM2 axis. CONCLUSIONS: Simvastatin can inhibit the HIF-1α/PPAR-γ/PKM2 axis, by suppressing PKM2-mediated glycolysis, resulting in decreased proliferation and increased apoptosis in HCC cells, and re-sensitizing HCC cells to Sora.

BACKGROUND: Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance. METHODS: Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. RESULTS: Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects. CONCLUSIONS: Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein. TRIAL REGISTRATION: ClinicalTrials.gov/NCT02406469.

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Microvesicles (MVs) derived from human mesenchymal stem cells (MSC MVs) were demonstrated to ameliorate inflammation in lungs. We have found their content of mRNA for keratinocyte growth factor was partly involved in their therapeutic effects. As MSC MVs also contained a substantial quantity of angiopoietin-1 (Ang-1) mRNA, which plays an essential role in vascular stabilization and resolving inflammation, we hypothesized that Ang-1 mRNA might similarly account for a part of their therapeutic effects. We downregulated Ang-1 mRNA expression in MVs, using a lentivirus vector carrying Ang-1 short hairpin RNA to transfect MSCs. A mouse model of lipopolysaccharide induced acute lung injury (ALI) was used in vivo. We also studied in vitro interactions between Ang-1 mRNA deficient MVs on macrophages and human lung microvascular endothelial cells. Compared with negative control, Ang-1 mRNA deficient MVs increased the influx of neutrophils and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid by 136% and 105%, respectively, suggesting a deteriorative lung inflammation and a failure to restore pulmonary capillary permeability assessed by Evan's blue dye and bronchoalveolar lavage albumin level. In vitro, the addition of Ang-1 mRNA deficient MVs failed to maintain the integrity of endotoxin-stimulated microvascular endothelial cells and abrogated the decrease in tumor necrosis factor-α level and the increase in interleukin-10 level mediated by negative control in RAW 264.7 cells. In summary, the therapeutic effects of MVs in ALI, and their immunomodulatory properties on macrophages were partly mediated through their content of Ang-1 mRNA. Stem Cells 2017;35:1849-1859.

Abstract Identification of early-stage pulmonary adenocarcinomas before surgery, especially in cases of subcentimeter cancers, would be clinically important and could provide guidance to clinical decision making. In this study, we developed a deep learning system based on 3D convolutional neural networks and multitask learning, which automatically predicts tumor invasiveness, together with 3D nodule segmentation masks. The system processes a 3D nodule-centered patch of preprocessed CT and learns a deep representation of a given nodule without the need for any additional information. A dataset of 651 nodules with manually segmented voxel-wise masks and pathological labels of atypical adenomatous hyperplasia (AAH), adenocarcinomas in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive pulmonary adenocarcinoma (IA) was used in this study. We trained and validated our deep learning system on 523 nodules and tested its performance on 128 nodules. An observer study with 2 groups of radiologists, 2 senior and 2 junior, was also investigated. We merged AAH and AIS into one single category AAH-AIS, comprising a 3-category classification in our study. The proposed deep learning system achieved better classification performance than the radiologists; in terms of 3-class weighted average F1 score, the model achieved 63.3% while the radiologists achieved 55.6%, 56.6%, 54.3%, and 51.0%, respectively. These results suggest that deep learning methods improve the yield of discriminative results and hold promise in the CADx application domain, which could help doctors work efficiently and facilitate the application of precision medicine. Significance: Machine learning tools are beginning to be implemented for clinical applications. This study represents an important milestone for this emerging technology, which could improve therapy selection for patients with lung cancer.

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66(Shc), and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.