Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Abstract Background & aim Esophageal squamous cell carcinoma (ESCC), a common disease in China, is mainly treated surgically. We established a prospective database of patients with esophageal cancer ...between January 2000 and December 2010, including 486 subjects with ESCC who underwent surgical treatment. In this study, we explored the prognostic significance of the expressions of HOXC6 and HOXC8, responsible for embryonic development, by studying the specimens collected from clinical subjects during strict follow-up periods. Materials & methods Immunohistochemistry was used to detect the expressions of HOXC6 and HOXC8 in 274 ESCC subjects including 138 ESCC subjects treated with surgery alone and 136 ESCC subjects treated with neoadjuvant chemotherapy. Survival analysis was performed from the day of surgery to August 2013. Results The 5-y survival rate of the 274 ESCC subjects was 44.2%, with a median survival time of 44.12 mo. For the 274 ESCC subjects involved in the investigation of HOXC6 and HOXC8 expressions, the median survival time of subjects with high-level expressions of HOXC6 and HOXC8 was shorter than that for subjects with low-level expressions ( P = 0.001, P < 0.001, respectively). Similar results were obtained from the analysis of the prognostic value of HOXC6 and HOXC8 in the group treated with surgery alone and the group treated with neoadjuvant chemotherapy. Multivariate analysis demonstrated that HOXC6 and HOXC8 expressions were independent prognostic factors in patients with ESCC. Conclusions The HOXC6 and HOXC8 genes can be used as prognostic markers in patients with ESCC, but prospective studies are still needed to confirm.
Abstract Objective Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary ...resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR. Methods Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC. Results The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5′-adenosine monophosphate–activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR. Conclusions The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.
Osteocalcin, a bone-derived polypeptide, was recently found to have hormonal function associated with metabolic disorders and atherosclerosis. Few studies have examined the association between ...circulating osteocalcin and coronary heart disease (CHD) risk. The aim of the present study was to investigate whether serum osteocalcin concentration was associated with CHD risk and metabolic profiles in Chinese adults. A total of 461 subjects (243 with CHD and 218 without CHD) who underwent coronary angiography were included. Serum osteocalcin, glucose, lipid profiles, and other biochemical markers were measured. Severity of coronary atherosclerosis was estimated by number of diseased vessels. Results showed that serum osteocalcin levels were significantly lower in the CHD group (12.2 ng/ml, 9.5 to 15.1) than in the non-CHD group (13.6 ng/ml, 10.7 to 18.0, p = 0.001) and were significantly decreased with the increasing of number of diseased vessels (p = 0.005). Serum osteocalcin concentration was inversely correlated with fasting and post load 2 hour plasma glucose and hemoglobin A1c (p = 0.044, 0.043, and 0.011, respectively), adjusting for CHD status. Odds ratios (95% confidence intervals) of CHD across increasing quartiles of serum osteocalcin were 0.68 (0.42 to 1.12), 0.59 (0.36 to 0.98), and 0.40 (0.23 to 0.69). The test for trend was significant (p = 0.0007). Adjusting for age, body mass index, and other conventional risk factors for CHD did not appreciably change the results. Spline regression analyses indicated a linear relation between serum osteocalcin level and CHD risk. In conclusion, our data indicate that serum osteocalcin level was associated with decreased risk of CHD and protective metabolic changes in Chinese adults.
Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
Population-level economic burden is essential for prioritizing healthcare resources and healthcare budget making in the future. However, little is known about the economic burden of lung cancer in ...China.
A prevalence-based approach was adopted to estimate the economic burden of lung cancer, including direct expenditure (medical and non-medical) and indirect cost (disability and premature death). Data on direct expenditure and work-loss days per patient in each year post-diagnosis were obtained from two primary surveys. Other parameters were obtained from literatures and official reports. Projections were conducted based on varying parameters. All expenditure data were reported in United States dollars (USD) using 2017 value (exchange rate: 1 USD= 6.760 CNY), with the discount rate of 3%.
The total economic burden of lung cancer was estimated to be 25,069 million USD in China in 2017 (0.121% of gross domestic productivity, GDP). The estimated direct expenditure was 11,098 million USD, up to 1.43% of total healthcare expenditure for China, covering 10,303 million USD and 795 million USD for medical and non-medical expenditure, respectively. The estimated indirect cost was 13,971 million, including 1,517 million USD due to disability and 12,454 million USD due to premature death. Under current assumptions, the projected total economic burden would increase to 30.1 billion USD, 40.4 billion USD, and 53.4 billion USD in 2020, 2025, and 2030, accounting for 0.121%, 0.131%, and 0.146% of China's GDP, respectively. However, if China meets the United Nation sustainable development goal of reducing premature death from non-communicable diseases by one-third by 2030, the total economic burden in 2030 would be 31.9 billion USD, 0.087% of China's GDP.
The economic burden of lung cancer in China in 2017 is substantial and more likely to increase significantly in the future. Policy makers need to take urgent actions in budget making for health systems. The economic burden could be alleviated by reducing the disease burden of lung cancer via effective control and prevention actions.
BACKGROUNDMediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's ...complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODSIn this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGSIn the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATIONFor mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDINGNational Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.
Abstract Background To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of ...spontaneous circulation (ROSC) by cardiopulmonary resuscitation. Methods CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. Results The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. Conclusion EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC.
Current study investigated the spatio-temporal distribution of fractional vegetation coverage (FVC) and climatic factors response in Three Gorges Reservoir area from 2000 to 2014 using a dimidiate ...pixel model. Several data sets were used including the MODIS NDVI data, land use/cover change (LUCC) data and past 15 years of FVC data. Our results suggested that, except 2006 the annual maximum FVC were stable from 2000 to 2014. Extremely arid climate in 2006 influences FVC of Three Gorges area. The annual average FVC of the study area was 91.28%. The monthly mean FVC showed a regular fluctuation, where mean higher FVC values were found from May to August and from December to March of the following years FVC was lower. Overall study area showed an upward trend of FVC from 2000 to 2014, basic invariant areas, slight increased areas and obvious increased areas were accounted for 84.70%, 8.75%, and 0.78% respectively, whereas significantly reduced areas and mild reduction areas were accounted for 1.52% and 4.25% FVC, respectively. The FVC growth areas were mainly distributed in the eastern part of the Three Gorges Reservoir area whereas degraded areas were mainly distributed in the hilly areas of the West and middle of the Three Gorges area. Greater than 2000 meters high mountains the FVC value reached 98.47%, and the slope greater than 25° the regional FVC value reached 92.60%. Strong correlations were observed between monthly mean temperature and FVC (R=0.88), precipitation and FVC (R=0.77), and growth season lag 1 month of FVC values and temperature (R=0.85).
Proteomics was used to identify a protein encoded by ORF 3a in a SARS-associated coronavirus (SARS-CoV). Immuno-blotting revealed that interchain disulfide bonds might be formed between this protein ...and the spike protein. ELISA indicated that sera from SARS patients have significant positive reactions with synthesized peptides derived from the 3a protein. These results are concordant with that of a spike protein-derived peptide. A tendency exists for co-mutation between the 3a protein and the spike protein of SARS-CoV isolates, suggesting that the function of the 3a protein correlates with the spike protein. Taken together, the 3a protein might be tightly correlated to the spike protein in the SARS-CoV functions. The 3a protein may serve as a new clinical marker or drug target for SARS treatment.
PDF
