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IntroductionDementia has become one of the significant causes of disability and dependency among older people globally. The proportion of people with dementia who are cared for at home has soared. The rapid growth of technology and data has stimulated artificial intelligence (AI) in patients with dementia at home. However, there are still tremendous opportunities and challenges in applying AI to patients with dementia at home, and there is no systematic overview.Methods and analysisThe review will adopt the Unified Theory of Acceptance and Use of Technology. This scoping review will follow the Joanna Briggs Institute scoping review methodology. The structure and content of this protocol follow the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews checklist. The proposed study will consider applying AI technology for dementia patients living at home and their families. Authors will conduct systematic searches: China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, China Biology Medicine disc, PubMed, CINAHL, Web of Science Cochrane database, EBSCO, Ovid, PsycINFO, Embase. The extracted data will be processed qualitatively and described through tables. The findings are integrated by a narrative synthesis. This review aims to evaluate the nature and extent of the application of AI technology in patients with dementia at home through a systematic search of the literature.Ethics and disseminationScoping review is an analysis of existing data and therefore does not require ethical approval. We will publish our findings in a peer-reviewed journal.Scoping review protocol registration . DOI:10.17605/OSF.IO/3NU9C.

Purpose To use medical record adjudication and predictive modeling methods to develop and validate an algorithm to identify anaphylaxis among adults with type 2 diabetes (T2D) in administrative claims. Methods A conventional screening algorithm that prioritized sensitivity to identify potential anaphylaxis cases was developed and consisted of diagnosis codes for anaphylaxis or relevant signs and symptoms. This algorithm was applied to adults with T2D in the HealthCore Integrated Research Database (HIRD) from 2016 to 2018. Clinical experts adjudicated anaphylaxis case status from redacted medical records. We used confirmed case status as an outcome for predictive models developed using lasso regression with 10-fold cross-validation to identify predictors and estimate the probability of confirmed anaphylaxis. Results Clinical adjudicators reviewed medical records with sufficient information from 272 adults identified by the anaphylaxis screening algorithm, which had an estimated Positive Predictive Value (PPV) of 65% (95% confidence interval [CI]: 60%-71%). The predictive model algorithm had a c-statistic of 0.95. The model's probability threshold of 0.60 excluded 89% (84/94) of false positives identified by the screening algorithm, with a PPV of 94% (95% CI: 91%-98%). The model excluded very few true positives (15 of 178), and identified 92% (95% CI: 87%-96%) of the cases selected by the screening algorithm. Conclusions Predictive modeling techniques yielded an accurate algorithm with high PPV and sensitivity for identifying anaphylaxis in administrative claims. This algorithm could be considered in future safety studies using similar claims data to reduce potential outcome misclassification.

Purpose To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. Methods Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1‐year baseline and minimum 6 months of follow‐up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. Results A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1–5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4–2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. Conclusions ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P

Chemoresistance is a major obstacle to prolonging pancreatic ductal adenocarcinoma (PDAC) patient survival. TET1 is identified as the most important epigenetic modification enzyme that facilitates chemoresistance in cancers. However, the chemoresistance mechanism of TET1 in PDAC is unknown. This study aimed to determine the role of TET1 in the chemoresistance of PDAC. TET1-associated chemoresistance in PDAC was investigated in vitro and in vivo. The clinical significance of TET1 was analyzed in 228 PDAC patients by tissue microarray profiling. We identified that TET1 downregulation is caused by its promoter hypermethylation and correlates with poor survival in PDAC patients. In vitro and in vivo functional studies performed by silencing or overexpressing TET1 suggested that TET1 is able to suppress epithelial-mesenchymal transition (EMT) and sensitize PDAC cells to 5FU and gemcitabine. Then RNA-seq, whole genome bisulfite sequencing (WGBS) and ChIP-seq were used to explore the TET1-associated pathway, and showed that TET1 promotes the transcription of CHL1 by binding and demethylating the CHL1 promoter, which consequently inhibits the Hedgehog pathway. Additionally, inhibiting Hedgehog signaling by CHL1 overexpression or the Hedgehog pathway inhibitor, GDC-0449, reversed the chemoresistance induced by TET1 silencing. Regarding clinical significance, we found that high TET1 and high CHL1 expression predicted a better prognosis in resectable PDAC patients. In summary, we demonstrated that TET1 reverses chemoresistance in PDAC by downregulating the CHL1-associated Hedgehog signaling pathway. PDAC patients with a high expression levels of TET1 and CHL1 have a better prognosis.

ObjectiveThis study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs).MethodsTumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells.ResultsTINs were primarily distributed in the intratumoral area, dendritic cells and NK cells were scattered evenly in intratumoral and stromal areas, and Tregs were rarely detected. The remaining 5 cell types were primarily present in peritumoral stroma. Total TINs (P < .001) and TAMs (P = .002) increased as NF-PanNET grade rose. Kaplan-Meier analyses showed that high intratumoral TINs, total TAMs, and stromal CD4+ T-cell infiltration correlated with shorter recurrence-free survival (RFS, P = .010, P = .027, and P = .035, respectively) and overall survival (OS, P = .017, P = .029, and P = .045, respectively). Additionally, high intratumoral CD8+ T cell infiltration correlated with prolonged RFS (P = .039). Multivariate Cox regression demonstrated that intratumoral TINs, World Health Organization (WHO) classification, and eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8th TNM) were independent factors for RFS (P = .043, P = .023, and P = .029, respectively), whereas intratumoral TINs and WHO classification were independent factors for OS (P = .010 and P = .007, respectively). Furthermore, the combination of TINs, WHO classification, and AJCC8th TNM remarkably improved prognostic accuracy for RFS. These results have been verified in the external validation set.ConclusionIntratumoral TINs are an independent and unfavorable predictor of postoperative NF-PanNETs. A combination of TINs, WHO classification, and AJCC8th TNM could improve prognostic accuracy for RFS.

Lipid metabolism is extensively reprogrammed in pancreatic ductal adenocarcinoma (PDAC). Stearoyl-coenzyme A desaturase (SCD) is a critical lipid regulator that was unexplored in PDAC. Here, we characterized the existence of cancer-associated fibroblasts (CAFs) with high SCD expression, and revealed them as an unfavorable prognostic factor. Therefore, primary CAFs and pancreatic cancer cells were harvested and genetically labeled. The mixture of CAFs and cancer cells were co-injected into scd

This study conducts a detailed analysis of the response of China's low-cost carriers (LCCs) to the threats posed by the pandemic from a route network perspective, aiming to explore the resilience of LCCs and Chinese airlines. Using geographic visualization and network analysis, we evaluate and compare the network connectivity of each Chinese LCC to see the change patterns, then elaborate on the network connection of Spring Airlines. The major results are: the LCC sector has not recovered, but some of them exceed the pre-pandemic levels in a less deregulated environment; different LCCs show different recovery patterns; Spring Airlines outperforms the other four LCCs in terms of network connectivity. The recovery process is supported by various external factors, such as the reduction of new confirmed COVID-19 local cases and international flights, the re-open of inter-provincial tour groups and tourism demand, the nationwide rebound activities promoted by the central government, and the supporting policies, especially new slot allocation processes issued by CAAC. The case study further indicates the effects of high-speed rail (HSR) and regional subsidy measures on the tactical actions of Springs in route planning. This paper serves as a referential case for the LCCs worldwide and has good application for the recovery of other LCCs in other countries. Moreover, the study conducted in this time window offers a chance to assess the development of Chinese airlines in a not fully deregulated aviation environment. It contributes to the debate on the theory of air network resilience.

China was the first market badly hit by the COVID-19 pandemic. This paper explores how Chinese airlines started and involved in labour charter operations, and tanalyse the evolutionary patterns of the charter route network. Flying charter flights for migrant workers is a unique phenomenon in China, especially during the Wuhan lockdown period. The main results are three: (1) private airlines were more active in charter operations during the earlier period, (2) labour charter operation is a newly appeared aviation-government-industry cooperative business model, and (3) there was a spread, change and shift of both charter flows and charter passengers during the four-week period of the study. This case study not only produces useful insights about the important role of charter flights in China during the Covid-19 pandemic period, but also contributes to the theory and practice related to aviation resilience. Also, it contributes to the discussion about aviation policies in China, taking labour charter operation as a window time to predicate future airline dynamics in a more deregulated environment. The results can help airlines, and airports adjust routes, distribute capacity, and adjust layouts for Spring Festival labour transport in normal or post-pandemic times.

In clinical medicine, patient drainage monitoring and early warning have received extensive attention from the clinical medical community since they reflect the real-time status of patients. Firstly, this study points out the shortcomings of current medical drainage technology combined with actual clinical applications and proposes a detailed analysis of the current medical drainage monitoring technology and medical drainage equipment. Secondly, this study focuses on cloud medical, intelligent medical and other digital intelligent medical development. Combined with advanced artificial intelligence technology and cloud data processing technology, this study is proposed to realize the clinical promotion, and popularization of medical drainage technology and promote the medical industry's attention to the realization of comprehensive and intelligent drainage monitoring.

Directional fluid transport is of significance to many physical processes in nature. How to manipulate this process by man-made material is still a key challenge to scientists. In this study, Janus fabric was constructed by electrospinning a layer of polyvinylidene fluoride (PVDF) nanofibers on woven cotton or gauze. The chemical composition, morphology and surface wettability of two sides of Janus fabric were characterized by infrared spectroscopy, scanning electron microscope (SEM) and contact angle measurement. By controlling the PVDF electrospinning time, the maximum hydrostatic pressure of Janus fabric with different PVDF thickness was measured. It was found that PVDF/gauze is more favorable for unidirectional water transportation, and the moisture also can transfer from hydrophobic side to hydrophilic side. With the advantages of facile preparation, low-cost and one-way water/moisture transportation, the Janus fabric prepared in this study can be applied for water separation, humidity transfer and water collection from the air.

Purpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI. Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy. Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.

•We estimate China domestic air passenger market's CO2 emissions in 2007 and 2014.•We assess the change of air route networks and emission features focused on regional disparity.•Applying decomposition method to identify the driving forces of estimated CO2 emissions.•Noteworthy offset to increasing CO2 emissions is indicated from modal split changes.

BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.MethodsTumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.ResultsTLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p8th TNM stage.ConclusionsThe presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.

Splenectomy is routinely performed during distal or total pancreatectomy (DP or TP) for pancreatic ductal adenocarcinoma (PDAC), but information about its oncological value is limited. TER cells, nonimmune cells discovered in the spleens of tumour-bearing mice, are elicited by tumours and promote tumour progression, while their role in the clinical outcomes of patients with PDAC remains unclear. In our study, postoperative specimens from 622 patients who underwent DP or TP with splenectomy were analysed by flow cytometry or immunofluorescence, and the relationship between splenic TER cell count and clinical parameters was calculated. We also purified human TER cells for functional experiments and mechanistic studies. We found that TER cell numbers were increased only in the spleens of patients with PDAC but not in PDAC tissue and adjacent pancreatic tissue. High splenic TER cell counts independently predicted poor prognosis (P < .001) and indicated large tumour size, lymph node metastasis, advanced 8th AJCC/mAJCC stage and high CA19-9 classification (all P < .050) in patients with PDAC. Mechanistic analysis showed that TER cells express artemin, which facilitates the proliferation and invasion of PDAC cells by activating GFRα3-ERK signalling. Our study reveals that TER cell count is an indicator of poor prognosis of PDAC, while splenectomy during pancreatic surgery might provide oncological benefits in addition to ensuring the radical resection of PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis. Many preoperative biomarkers can predict postoperative survival of PDAC patients. In this study, we created a novel ratio index based on preoperative liver function test, γ‐glutamyltransferase‐to‐albumin ratio (GAR), and evaluated its prognostic value in predicting clinical outcomes of PDAC patients following radical surgery. We retrospectively enrolled 833 PDAC patients who had underwent radical surgery at our institution between January 2010 and January 2017. Patients were divided into two groups according to the cut‐off value of GAR. Univariate and multivariate survival analysis between the groups were evaluated. TNM stage, GAR, preoperative serum carbohydrate antigen 19‐9 (CA19‐9) and tumor differentiation were combined to generate a more accurate prognostic model. The optimal cut‐off value of GAR was 0.65. Significant correlations were found between GAR and tumor location, tumor size, vascular invasion, obstructive jaundice, biliary drainage and parameters of liver function test. Univariate and multivariate analysis showed that high level of GAR independently predicted poorer postoperative overall survival (OS, P < 0.001) and recurrence‐free survival (RFS, P < 0.001). Subgroup analysis demonstrated that GAR was predictive of survival in patients without biliary obstruction or severely impaired liver function. In addition, integration of GAR, preoperative serum CA19‐9, and tumor differentiation into TNM staging system could better stratify the prognosis for PDAC patients compared with TNM stage alone. Our study demonstrates that preoperative GAR is an independent prognostic factor for prediction of surgical outcomes in PDAC patients. Combination of TNM stage, GAR, preoperative serum CA19‐9, and tumor differentiation can enhance the prognostic accuracy.

Jiaju Tibetan Village, located in Danba country, Sichuan province, is a newly developed ethic tourism destination. Based on the case study of house renovation and reconstruction, this paper studies the processes of local community participating in tourism development, and analyzes the impacts of local community’s participation on forming destination image as well as destination brand. The study methods applied in this paper are building measurement, questionnaire survey and interview with villagers. The results show that villagers have focused on selecting the icons of Gyarong Tibetan culture during the process of house re-construction and presented these icons to the tourists. It is found out that local community has contributed to Jiaju village by selecting a plain destination image and building a higher quality brand. Also, villagers have improved their living environment through the house reconstruction.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are a vital constituent of the tumor microenvironment (TME) and have several activities, but the effect of CAF heterogeneity on the molecular features and clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: An algorithm “scFrac” based on single-cell sequencing data from the Gene Expression Omnibus was introduced to emulate the enrichment of CAF subtypes in a TCGA-PDAC cohort and their prognostic influence, and confirmed by an external validation group (66 patients with PDAC) with multiplex immunohistochemistry staining. A comprehensive analysis including metabolic profile and transcription factor regulon activity was carried out among CAF subtypes. RESULTS: Three distinct CAF populations were confirmed: myofibroblast (myCAF), inflammatory CAF (iCAF), and antigen-presenting CAF (apCAF). These subtypes expressed distinct metabolic profiles and transcriptional regulon activity. KEGG pathway annotation demonstrated that complement and coagulation cascades, as well as cytokine-cytokine receptor interaction were dominant in iCAFs, and pathways related to focal adhesion, and ECM-receptor interaction showed dominance in myCAFs, while antigen processing and presentation were the top enriched pathways in apCAFs. iCAFs trended to glycolysis with CREB3L1, EGR2 and SOX4 activation, whereas myCAFs depend on the tricarboxylic acid cycle and its derivatives with NRF2, CEBPD and YBX1 activation. iCAF is a protective factor associated with an inflammatory phenotype, but myCAF is an important factor in the poor prognosis of PDAC. CONCLUSIONS: We identified distinct molecular characteristics of 3 CAF subtypes in PDAC and plotted their metabolism profile. We introduced a novel algorism, scFrac, for exploring how CAF subgroups dysregulate cancer biology, and also shed a new therapeutic light on targeting the CAF subtype in TME.

This paper reviews the changes in cross-strait aviation policies that have occurred since 2009 and assesses the effects of those changes on tourism flows, focusing on the routes served by charter flights. This study is unique because it explores the linkage between aviation and tourism policies in a newly established market. Based on three distinct sets of time series data from 2009 to 2015, various statistics and vector autoregression methods are applied to examine the impacts of the changes on tourism as well as the relationships among scheduled services, charter services, and tourism flows. Our main findings are as follows: First, the changes have promoted scheduled services constantly and aggressively, which contributed to the transformation of cross-strait tourism into a thriving business. Second, through regulation, the changes have created a policy framework for charter flight business. Third, charter flights have become a supplement to scheduled flights in the tourism market. Our contribution is threefold. First, our study contributes to the literature on the effect of aviation policy regimes on the tourism market with respect to charter operations. Second, it provides practical guidance for regions with similar situations, such as the Korean Peninsula. Third, it has crucial policy implications for regulators and governments and provides advice for airlines in the cross-strait market.

Radical surgical resection represents the only hope of cure for pancreatic neuroendocrine tumor (PanNET). Adjuvant therapy is rarely used because there is no evidence to distinguish patients with high recurrence risk. Here we investigated the recurrence feature of resected PanNET and established a novel risk stratification to predict its recurrence. We analyzed 505 PanNET patients who underwent R0 resection at our institute from January 2004 through May 2015. The median follow-up was 71months (range: 12months-143months), 129 patients (25.5%) experienced recurrence with median disease-free survival (mDFS) of 19months. Restricted cubic spline (RCS) functions revealed a positive, linear relationship between Ki-67 index and recurrence. Multivariate analysis showed T stage, N stage, insulinoma and Ki-67 index were independent predictors of recurrence (P

Effect of atorvastatin inhibition of endoplasmic reticulum stress and amelioration of atherosclerosis through AMPK pathway were studied. Eight-week-old male apolipoprotein E-deficient (ApoE−/−) mice were fed with high-fat diet for 2 weeks and randomly divided into two groups: Atorvastatin treatment group was given atorvastatin (5 mg/kg/day) injection for a total of 6 weeks; control group was given the same dose of PBS through intraperitoneal injection for a total of 6 weeks. H&E staining was used to detect plaque size; immunohistochemical staining was used to detect T cells, macrophages and phospho-protein kinase-like ER kinase (phospho-PERK) in localized plaques. Proteins were extracted from mouse thoracic and abdominal aortic tissues. Western blot analysis was used to detect the protein expression levels of endoplasmic reticulum stress-related molecules phospho-eukaryotic initiation factor-2α (p-eIF2α), eukaryotic initiation factor (eIF2a), and sliced x-box binding protein 1 (sXBP-1). Cultured human umbilical vein endothelial cells (HUVECs), induced endoplasmic reticulum stress with human oxidized low density lipoprotein (ox-LDL), were treated with atorvastatin, AMPK agonist 5-amino-4-imidazolecarboxamide riboside-I-β-D-ribofuranoside (AICAR) and AMPK-DN that expressed a dominant-negative mutant of AMPK. Western blot analysis was used to test the expression levels of endoplasmic reticulum stress-related molecules p-elF2a and sXBP-1. The area of aortic plaques in atorvastatin group was obviously decreased, and the infiltrations of CD3+ T cells and macrophages in the localized plaques were reduced. The endoplasmic reticulum stress-related proteins sXBP-1 and p-eIF2a were significantly reduced. The results of immunohistochemistry also showed a significant decrease in the level of phospho-PERK (p-PERK) in atorvastatin group. The results in ox-LDL-induced HUVECs showed that atorvastatin inhibited ox-LDL-induced endoplasmic reticulum stress, and the AMPK agonist AICAR also had the same effect, which was offset by DN-AMPK treatment. Atorvastatin inhibits ER stress both in vitro and in vivo and this protective effect is mediated by AMPK activation.

We aimed to investigate the effects of CX-C chemokine receptor type 4 (CXCR4) on transforming growth factor (TGF)-β1-induced cardiac fibrosis in Human cardiac fibroblasts (HCFs). HCFs were stimulated with TGF-β1, and the level of α-smooth muscle actin (α-SMA) was assessed by immunofluorescence assay. The expression of CXCR4 was detected by Western blotting. Then the cells were incubated with CXCR4 antagonist AMD 3465. Cell viability was measured by CCK-8 assay. The expression of α-SMA, proliferating cell nuclear antigen (PCNA) and Ki67 were examined. Collagen synthesis was detected by sirius red staining. Moreover, the expression of phpspho-Smad2 (p-Smad2) and p-Smad3 were determined. We found that the level of α-SMA was increased after induction with TGF-β1. The expression of CXCR4 was upregulated in TGF-β1-treated HCFs. Following treatment with AMD 3465, cell proliferation was inhibited coupled with a decrease in PCNA and Ki67 expression. Additionally, the expression of α-SMA was decreased after being intervened with AMD 3465. Concurrently, the levels of collagen were reduced accompanied by downregulation of Collagen I and III. Furthermore, AMD 3465 treatment decreased the expression of p-Smad2 and p-Smad3. Our findings suggested that CXCR4 antagonist AMD 3465 could alleviate cardiac fibrosis via blocking TGF-β1-induced activation of Smad2/3 in HCFs.

Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). We found that the incidence of DKA was 55.5 per 1000 person-years in US commercially insured patients with T1DM; age-sex-standardized incidence decreased at an average annual rate of 6.1% in 2018–2019 after a steady increase since 2011.

Purpose Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users. Methods We used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose. Findings Overall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years). Implications Concomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.

In the process of urbanization, the gradual loss of the characteristics of traditional villages caused by the destruction of environmental resources calls for the attention to return to pursue the essence of traditional village architecture as well as traditional building renovation and environmental coordination. Through the study of the characteristics, craftsmanship and aesthetics of the local materials, the transformation and design of the local buildings with the theory of oriental design are used to show the coexistence of the local customs, architectural characteristics and natural environment. Through the experimental study on the application of local materials in this paper, the design strategy of local materials for the transformation of traditional buildings is summarized to protect and inherit Chinese local buildings, which has a deep developmental significance to the transformation and application architectures in future.

Many Chinese cities have completed barrier-free transportation infrastructures system but always ignore its efficiency. The study purpose of this research is to find out some community planning method to improve the effect of bus and metro barrier-free transportation system in China. Filed survey are research methods used. Taking Chengdu as the study area, researchers carried out a large scale filed survey to study the current bus and metro barrier-free systems. Through relevant literature research, then find people physically challenged to check whether these infrastructure meet their really need. Finally, based on considerable empirical evidence, the findings can be generalized to suggest five issues relevant to the creation of ‘enabling’ or more accessible city environments for all. Overall, this study provides academic support and empirical analysis for what was ignored in urban transportation planning (UTP) process owing to efficiency first principle.

The Civil Aviation Administration of China (CAAC) started to open commercial airlines sector to private, collective and foreign capitals in 2004. From 2004 to 2007, 14 airlines were given approval to operate domestic passenger flights, which brought researchers a vital chance to investigate the performance of local state-owned airlines or private airlines in aviation sector. The study purposes of this paper are (1) to review the development process of these newly established airlines, and (2) to examine their air-route networks’ change patterns. The results show that, generally, the airlines have been re-constructing its air-route networks over those years. High-speed rail (HSR) operation is one of key elements to explain the change patterns. The study results are useful for aviation policy makers, airlines stockholders, and capitals interested in Chinese aviation market.

• This study explores the effects of charter promotions on international tourism in Japan.

Background The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery. Methods Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort. Results CD15+ neutrophils, CD20+ B cells and CD206+ tumour-associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence-predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3·63, 95 per cent c.i. 2·18 to 6·04; P < 0·001) and recurrence-free (HR 2·93, 1·81 to 4·75; P < 0·001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound-guided fine-needle aspiration. Conclusion PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevanceThe immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4.This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.

Low-carbon urban development is a hot spot of global concerns for fighting against climate change for China, transportation sector has a significant contribution to urban CO 2 emissions, while the emissions are still increasing. Transit-Oriented Development (TOD) strategies provide a novel approach for urban planners to facilitate the urban carbon mitigation from transportation sector in long-term. While TOD strategies are emerging cases, they are merely qualitatively discussed in China, lacking practical indicators and quantitative verification for supporting the real urban plan. With such circumstance, this study aims to conduct an empirical and quantitative study on the applications of TOD strategy in Shanghai based on Exploratory Spatial Data Analysis (ESDA) and the updating data. Firstly, the changes of urban morphology were quantitatively analyzed by spatial cluster analysis, which reveals the layer structure changes and residents migration at about 1 km accuracy. Secondly, accessibility was selected as an indicator for urban transportation and estimated by method based on Time Cost Weighted Distance. Finally, the effectiveness of TOD was investigated by evaluating the integration between population and transportation accessibility with Geographic Weighted Regression model. Results highlight that TOD can effectively improve the transportation network with higher accessibility and lower urban carbon emissions. The outcomes of this study provide critical insights to the recent practice in Shanghai, as well as the practical guidance to low carbon urban planning in developing countries.

Pancreatic cancer is an aggressive and devastating disease that is characterized by uncontrolled progression, invasiveness and resistance to conventional treatment. In the past decades, much effort has been given to cancer genetics and pathological classification of this disease. Our previous study has uncovered a subgroup of patients with poor outcome, which is characterized by serum signature of CEA(+)/CA125(+)/CA19-9 ≥ 1000 U/mL; however, the underlying biology mechanism remains poorly understood. By using high-throughput screening analysis, we analyzed gene expression signature in highly malignant patients with serum markers of CEA(+)/CA125(+)/CA19-9 ≥ 1000 U/mL. Multiple differentially expressed genes were identified, many of which were closely related with cancer metabolic changes. Treatment of pancreatic cancer cell lines PANC-1 with transforming growth factor-β (TGF-β), which was commonly used to induce metastasis, has uncovered that the glycolytic process and antioxidant response was up-regulated upon TGF-β stimulation. These results were consistent with the high-throughput screening analysis. Subsequent analysis indicated that among glycolytic genes, aldolase A (ALDOA) increased the most significantly upon TGF-β treatment. Further in vitro and in vivo results demonstrated that ALDOA was associated with proliferation and metastasis of pancreatic cancer cells. Moreover, ALDOA predicted poor prognosis of pancreatic cancer, partially due to its role in E-cadherin expression regulation, and the results were further validated by analysis of the correlation between ALDOA and E-cadherin expression in pancreatic cancer tissue samples. Mechanistically, the role of ALDOA in pancreatic cancer might attribute to its regulation of c-Myc, HIF1α and NRF2 (Nuclear Factor, Erythroid 2-Like 2), which were key regulators of glycolysis and antioxidant response control.

Refereed/Peer-reviewed This paper examines China's LCC market and assesses the network development patterns from a geographical perspective. Overall, a nationwide LCC network has been formed with each individual LCC focusing on their own markets with limited overlap to avoid cut-throat competition. Spring Airlines has developed an advanced network supported by its core bases including Shanghai in East China, Shijiazhuang in North China, Shenyang in Northeast China and Shenzhen in South China. China United has developed a network radiating from Beijing. West Air and Lucky Air seem to be developing a hub-and-spoke network that contributes to the tourism industry in West China. The LCC network is affected by seasonal variations, especially for the routes to tourism destinations such as Haikou, Sanya and Xiamen. Hub cities, however, experience less seasonal impact. This research also finds that routes between 600 and 1800 km account for a large proportion of the LCC markets. Aviation policy, local government's subsidization and the expansion of the high-speed rail network have helped shape the landscape of China's LCC sector. usc

Purpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI. Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy. Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.

The clinicopathological and prognostic features of insulinoma with synchronous metastases are unclear. This study aimed to verify the distinct clinicopathological and prognostic features of insulinoma with synchronous distant metastasis.Patients with pancreatic neuroendocrine tumor (PanNET) were retrospectively enrolled and divided into cohort 1 (Fudan University Shanghai Cancer Center) and cohort 2 (Surveillance, Epidemiology, and End Results Program database). Both cohorts were further divided into three subgroups: insulinoma, nonfunctioning pancreatic neuroendocrine tumor (NF-PanNET), and non-insulinoma functioning pancreatic neuroendocrine tumor (NiF-PanNET).Cohorts 1 and 2 comprised 505 and 2761 patients (1566 M0 patients and 1195 M1 patients), respectively. In cohort 1 and cohort 2 M0 subgroup, insulinoma showed longer disease-free survival, overall survival (OS), and disease-specific survival (DSS) than NiF-PanNET and NF-PanNET (not reached vs. 48 and 60months, p 0.001; 183months vs. 87 and 109months, p 0.001; 247months vs. 121 and 140months, p = 0.002). However, in cohort 2 M1, the mDSS for metastatic insulinoma was shorter than that for NiF-PanNET (31months vs. 61months, p = 0.045), while the mDSS and mOS were similar to those for NF-PanNET. The percentage of T1 and N0 patients was similar between the metastatic insulinoma subgroup and NiF-PanNET and NF-PanNET subgroups. The Ki-67 index and recurrence had a positive linear relationship only for NiF-PanNET and NF-PanNET (p = 0.009).Insulinoma with synchronous metastasis showed clinicopathological and prognostic characteristics similar to those of NF-PanNET. Metastatic insulinoma had worse prognosis than non-insulinoma F-PanNET. These findings may help in the clinical management of metastatic insulinoma.

Higenamine, a plant-based alkaloid, exhibits various properties, such as antiapoptotic and antioxidative effects. Previous studies proved that higenamine possesses potential therapeutic effects for ischemia/reperfusion (I/R) injuries. However, the role of higenamine in cerebral I/R injury has not been fully evaluated. Therefore, we aimed to investigate the effect of higenamine on cerebral I/R injury and the potential mechanism. Our data showed that higenamine ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal cells injury. Induction of reactive oxygen species and malonaldehyde production, and the inhibition of superoxide dismutase and glutathione peroxidase activity caused by OGD/R were attenuated by higenamine. In addition, higenamine inhibited the increases in caspase-3 activity and Bax expression, and inhibited the decrease in Bcl-2 expression. Furthermore, higenamine elevated the expression levels of p-Akt, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitor of PI3K/Akt (LY294002) abolished the protective effects of higenamine on OGD/R-induced neuronal cells. These findings indicated that higenamine protects neuronal cells against OGD/R-induced injury by regulating the Akt and Nrf2/HO-1-signaling pathways. Collectively, higenamine might be considered as new strategy for the prevention and treatment of cerebral I/R injury.

The objective of this study was to compare the risks of breast cancer in women treated with insulin glargine and NPH using claims data. The MarketScan and Clinformatics databases were used to identify patients prescribed glargine or NPH in the study periods of January 2007 to March 2016 and July 20to June 2016, respectively. The risks of breast cancer in patients prescribed glargine relative to NPH were compared using three approaches: (1) on-treatment, (2) intent-to-treat and (3) time-dependent analysis. The overall and follow-up period stratified adjusted hazard ratios (aHRs) for breast cancer for glargine compared to NPH were obtained using Cox proportional hazards modelling controlling for potential confounders.In the MarketScan database, 75,422 glargine and 21,491 NPH patients were identified, of which 42,491 glargine and 7,826 NPH patients were new users. Using the Clinformatics database, 65,648 glargine and 16,194 NPH patients were identified, including 47,118 and 10,560 new users, respectively. The overall aHRs for breast cancer for glargine compared to NPH ranged from 0.90 (95% CI: 0.76-1.07) in the time-dependent analysis for all users in the Clinformatics database to 1.30 (95% CI: 0.76-2.25) in the on-treatment analysis for new users in the MarketScan database. In the MarketScan database, the aHRs stratified by the follow-up period (< 1, 1 - < 3, 3 - < 5 and ≥ 5 Years) ranged from 0.67 to 1.63. In the Clinformatics database the corresponding aHRs ranged from 0.85 to 1.40. All 95% confidence intervals (CIs) included the null value of 1. These findings suggest that the risk of breast cancer in patients prescribed glargine was not different from that in NPH patients. In conclusion, the risks of breast cancer were not different between patients prescribed glargine and NPH. Additionally, no association between glargine and breast cancer was observed with follow-up longer than 5 years. Disclosure P. Boyle: Other Relationship; Self; Sanofi. C. Wu: Employee; Self; Sanofi. K. Sharma: Employee; Spouse/Partner; Sanofi US. S.L. Lin: Employee; Self; Sanofi. Employee; Spouse/Partner; Bristol-Myers Squibb Company. J. Juhaeri: Employee; Self; Sanofi. Other Relationship; Spouse/Partner; Sanofi.

Pancreatic cancer is currently one of the deadliest solid malignancies and pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. In the past decade, diagnostics and surgical techniques for PDAC have been evolving steadily; however, clinical outcomes of patients with PDAC have shown little, if any, improvement. Subgroup classification based on accurate prediction of prognosis in patients with pancreatic cancer is important for treatment selection and clinical decision-making. The traditional method to evaluate prognosis relies on the TNM staging system, but it may not reflect the true status of every patient due to individual biological differences. Metabolomics is a field of study that involves the identification and quantification of metabolites present in a biological system. Analysis of metabolic differences between cancerous and noncancerous tissues can provide novel insights into tumor biology that are closely associated with disease prognosis and diagnosis. Therefore, evaluation of metabolic tumor burden may improve the accuracy of the clinical decision-making process, thereby facilitating optimization of the treatment strategies for pancreatic cancer.

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high-volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19-9 independently indicated surgical response in pancreatic cancer. Patients with CA19-9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19-9 levels decreased postoperatively. CEA and CA125 in the presence of CA19-9 ≥1000 U/mL could independently predict the non-decrease of CA19-9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p

Background— A simple risk score to predict long-term mortality after percutaneous coronary intervention (PCI) using preprocedural risk factors is currently not available. In this study, we created one by simplifying the results of a Cox proportional hazards model. Methods and Results— A total of 11 897 patients who underwent PCI from October through December 2003 in New York State were randomly divided into derivation and validation samples. Patients’ vital statuses were tracked using the National Death Index through the end of 2008. A Cox proportional hazards model was fit to predict death after PCI using the derivation sample, and a simplified risk score was created. The Cox model identified 12 separate risk factors for mortality including older age, extreme body mass indexes, multivessel disease, a lower ejection fraction, unstable hemodynamic state or shock, several comorbidities (cerebrovascular disease, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and renal failure), and a history of coronary artery bypass graft surgery. The C statistics of this model when applied to the validation sample were 0.787, 0.785, and 0.773 for risks of death within 1, 3, and 5 years after PCI, respectively. In addition, the point-based risk score demonstrated good agreement between patients’ observed and predicted risks of death. Conclusions— A simple risk score created from a more complicated Cox proportional hazards model can be used to accurately predict a patient’s risk of long-term mortality after PCI.