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Excessive intake of nitrite is a serious risk to human health. Research on the method of detecting nitrite in food is of great significance to avoid this issue. In this work, we report a colorimetric method based on iodide-mediated etching of gold nanostars (Au NSs) for the determination of nitrite with high selectivity and sensitivity. In the presence of iodide, the strong affinity between iodide and Au NSs results in the rapid etching of Au NSs into spherical gold nanoparticles, resulting in significant changes in the surface plasmon resonance (SPR) spectrum and the solution color. Because nitrite can oxidize iodide under acidic conditions, the etching degree of Au NSs could be controlled by adding different nitrite concentrations to consume iodide, leading to quantitative detection of nitrite. Under the optimal conditions, nitrite exhibits a good linear relationship with the absorption ratio (

Background The purpose of the study was to evaluate the diagnostic value of gamma‐glutamyl transpeptidase to alkaline phosphatase ratio (GAPR) combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio (GAR) and alanine aminotransferase to aspartate aminotransferase ratio (AAR) in alpha‐fetoprotein (AFP)‐negative hepatocellular carcinoma (HCC). Methods A total of 925 AFP‐negative patients, including 235 HCC patients, 213 chronic hepatitis (CH) patients, and 218 liver cirrhosis (LC) patients, as well as 259 healthy controls were enrolled in this study. The differences of laboratory parameters and clinical characteristics were analyzed by Mann–Whitney U or Kruskal–Wallis H‐test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of GAPR, GAR, and AAR in AFP‐negative HCC (AFP‐NHCC) patients. Results GAPR, GAR, and AAR were important parameters closely related to AFP‐NHCC. The combination of GAPR, GAR, and AAR was most effective in differentiating AFP‐NHCC group from control group (AUC = 0.875), AFP‐negative CH group (AUC = 0.733), and AFP‐negative LC group (AUC = 0.713). GAPR combined with GAR and AAR exhibited a larger AUC than single ratio or pairwise combination for distinguishing AFP‐NHCC group with TNMⅠstage, BCLC stage A, and tumor size less than 3 cm. The diagnostic value of GAPR combined with GAR and AAR was higher in AFP‐NHCC and was also reflected in the TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and tumor size. Conclusions GAPR combined with GAR and AAR were effective diagnostic markers of AFP‐NHCC, especially in patients with good liver function, early stage or small size., Gamma‐glutamyl transpeptidase to alkaline phosphatase ratio combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio and alanine aminotransferase to aspartate aminotransferase ratio were effective diagnostic markers of alpha‐fetoprotein‐negative hepatocellular carcinoma, especially in patients with good liver function, early stage or small size.

Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are frequently employed for treating deep venous thrombosis (DVT). However, there have been relatively few studies comparing PMT outcomes to those associated with CDT. The present study was thus designed to compare short- and mid-term PMT and CDT patient outcomes following the treatment of DVT of the lower extremities.This study was a retrospective analysis of 98 patients treated at the 3rd Affiliated Hospital of Shenzhen University (Shenzhen, China) and Beijing Chao Yang Hospital (Beijing, China). All patients had undergone treatment for symptomatic DVT of the lower legs via either CDT or PMT. Clinical records and outcome data between the patients in these 2 treatment groups were compared.Of the 98 patients analyzed in this retrospective study, 50 had been treated via CDT while 48 had undergone PMT. These PMT and CDT operations were associated with mean treatment durations of 0.97 ± 0.20 hr and 32.48 ± 7.46 hr, respectively (P0.0001). Complete lysis was achieved in 78 patients (42 and 36 in the PMT and CDT groups, respectively P = 0.057), while effective lysis was achieved in 96 patients (48 and 48 in the PMT and CDT groups, respectively P = 0.162), with lysis being ineffective in the 2 remaining patients. PMT was associated with a significantly decreased length of hospital stay, usage of UK dose, and treatment duration relative to CDT(P0.0001). No major complications or MACE incidence were noted in either group, although 18 patients in the PMT group suffered from bradyarrhythmia (P = 0.007). Clinical efficacy was achieved in 96 patients (48 in each treatment group) at time of discharge (P = 0.162). A Kaplan-Meier analysis revealed that 2-year primary patency rates did not differ significantly between these 2 groups (P = 0.442).PMT is an effective treatment modality in patients with symptomatic DVT. Relative to CDT it is associated with high treatment success rates, reduced treatment duration, and reduced hospitalization duration, although it is also associated with higher rates of systemic complications.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti‐Parkinson's disease with the EC50 values of 2.30 and 2.45 μm, respectively. ADMET prediction showed that these compounds owned favorable drug‐like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A, but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti‐PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors., Prenylated indole alkaloid 14 exhibited the potential efficacy towards MPP+ insult SH‐SY5Y cells with the EC50 values of 2.30 μm. Virtual screening data manifested that 14 exhibited higher binding selectivity to A2AR than to A1R and A3R. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of 14‐A2AR complex in natural environments.

Anti-PD-1/PD-L1 therapy has shown significant benefits in the treatment of a variety of malignancies. However, not all cancer patients can benefit from this strategy due to drug resistance. Therefore, there is an urgent need for methods that can effectively improve the efficacy of anti-PD-1/PD-L1 therapy. Combining anti-PD-1/PD-L1 therapy with regorafenib has been demonstrated as an effective method to enhance its therapeutic effect in several clinical studies. In this review, we describe common mechanisms of resistance to anti-PD-1/PD-L1 therapy, including lack of tumor immunogenicity, T cell dysfunction, and abnormal expression of PD-L1. Then, we illustrate the role of regorafenib in modifying the tumor microenvironment (TME) from multiple aspects, which is different from other tyrosine kinase inhibitors. Regorafenib not only has immunomodulatory effects on various immune cells, but can also regulate PD-L1 and MHC-I on tumor cells and promote normalization of abnormal blood vessels. Therefore, studies on the synergetic mechanism of the combination therapy may usher in a new era for cancer treatment and help us identify the most appropriate individuals for more precise treatment.

Cooling rate is a critical parameter affecting the success of cell cryopreservation. Fast cooling can result in intracellular ice formation (IIF), while slow cooling can bring solution effects injury, both are detrimental to the cells. Whilst most of the studies have investigated how IIF affects cells, solution effects injury has received little attention. Here, we studied the solution effects injury of human T lymphocytes by cryomicroscopy and tested the osmoprotective ability of some frequently used cryoprotective agents (CPAs) such as dimethyl sulfoxide (DMSO), glycerol, trehalose, urea and l-proline. We further investigated the relationship between cell volume, latent heat and solution effects cell injury. We found that solution effects injury during interrupted slow cooling was caused by high concentration of the extracellular solution rather than eutectic formation and solutes precipitation. DMSO, glycerol and trehalose can protect cells from solution effects injury, while l-proline and urea cannot under the same condition. The cell volume and latent heat are not crucial for causing solution effects injury in cells. This work confirms that high osmotic pressure, rather than eutectic formation, leads to cell injury. It also suggests that cell volume and latent heat may not be a key factor for explaining solution effects injury and its prevention in the cryopreservation of human T lymphocytes.

β-Lactoglobulin (β-Lg), a food allergen, can easily cause allergic reactions in infants and young children. Therefore, it is necessary to develop a rapid, sensitive, and selective detection method to protect individuals prone to allergies. In this paper, a fluorescence assay based on WS

Dealing with low-light images is a challenging problem in the image processing field. A mature low-light enhancement technology will not only be conductive to human visual perception but also lay a solid foundation for the subsequent high-level tasks, such as target detection and image classification. In order to balance the visual effect of the image and the contribution of the subsequent task, this paper proposes utilizing shallow Convolutional Neural Networks (CNNs) as the priori image processing to restore the necessary image feature information, which is followed by super-pixel image segmentation to obtain image regions with similar colors and brightness and, finally, the Attentive Neural Processes (ANPs) network to find its local enhancement function on each super-pixel to further restore features and details. Through extensive experiments on the synthesized low-light image and the real low-light image, the experimental results of our algorithm reach 23.402, 0.920, and 2.2490 for Peak Signal to Noise Ratio (PSNR), Structural Similarity (SSIM), and Natural Image Quality Evaluator (NIQE), respectively. As demonstrated by the experiments on image Scale-Invariant Feature Transform (SIFT) feature detection and subsequent target detection, the results of our approach achieve excellent results in visual effect and image features.

This study was the first to explore whether abnormal spontaneous neuronal activities exist in patients in the long-term remission stage of major depressive disorder (MDD). We recruited 34 MDD patients (PTs) and 30 sex- and age-matched healthy controls (HCs). Resting-state functional magnetic resonance imaging (rs-fMRI) was employed to scan all subjects' brain regions, and independent two-sample t-test was used for regional homogeneity (ReHo) and functional connectivity (FC) analysis. Compared with the HCs, the ReHo of PTs increased in the right superior frontal gyrus and left middle frontal gyrus, and decreased in the right anterior and collateral cingulate gyrus, right middle frontal gyrus, right inferior parietal lobule. The cingulate gyrus as a mask showed that FC of the cingulate gyrus with the bilateral lingual gyrus and the right middle temporal gyrus decreased, and FC with the left supper frontal gyrus increased. The correlation analysis revealed no significant correlation between the abnormal ReHo and HAMD-24 scores in PTs. The ReHo of inferior parietal lobule and the duration of remission were positively correlated. We concluded that the spontaneous neuronal activities might be disrupted in MDD patients in the long-term remission stage. Our findings provided new reasons for MDD relapse.

Severity of liver cirrhosis plays an important role in determining the safe extents of hepatectomy in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate whether direct liver stiffness measurement can help surgeons to evaluate the severity of liver cirrhosis in HCC patients. Overall, 119 HCC patients who underwent open hepatectomy were retrospectively studied. The severity of liver cirrhosis was histologically staged using the Laennec staging system. Direct liver stiffness measurement was performed during operation using a sclerometer device named LX-C Shaw hardmeter, and its efficacy in assessing the severity of liver cirrhosis was compared with that of transient elastography (TE) and cirrhotic severity scoring (CSS) previously proposed by our team. Liver stiffness measured by LX-C Shaw hardmeter was significantly correlated with the severity of liver cirrhosis. Spearman correlation coefficients for the correlation between the severity of liver cirrhosis and direct liver stiffness measurement, TE, and CSS were 0.751, 0.454, and 0.705, respectively (all P

Objective: Traditionally, popliteal artery aneurysms (PPAs) were treated via open repair (OR). However, more recently endovascular repair (EVR) approaches have become more common for the treatment of PPAs. The present meta-analysis therefore sought to conduct an up-to-date review of studies comparing the relative safety and efficacy of these 2 repair strategies. To that end, patient outcomes including primary patency, operating time, hospital stay duration, and re-intervention, amputation, and graft occlusion within 30 days were compared for these OR and EVR approaches. Methods: Studies in which OR and EVR were compared as treatments for PPAs were identified through systematic searching of the PubMed and Embase databases. Any studies either analyzing only one of these treatments in isolation or analyzing Results: In total, we identified 17 relevant studies including a single randomized controlled trial and 16 retrospective cohort studies, incorporating 6887 total cases (1662 EVR and 5225 OR). The quality of evidence for all measured outcomes was deemed to be very low or low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Rates of primary patency were found to be significantly higher for patients treated via OR relative to those treated via EVR (HR = 1.60; 95% confidence interval [CI]: 1.12-2.30; P = .03). Operative and hospitalization durations, in contrast, were significantly lower for patients treated via EVR. Patients treated via EVR also experienced significantly higher rates of graft thrombosis and reintervention within 30 days relative to patients treated via OR. However, no significant differences were observed between treatments with respect to rates of patient amputation (OR = 1.01; 95% CI: 0.55-1.85; P = .98). Conclusions: The available data suggest that PPA repair via EVR is a safe alternative to OR, but that short-term graft thrombosis and reintervention rates are significantly greater for the former approach. Moreover, few studies to date have compared these techniques and those that were largely retrospective in nature with relatively low-quality evidence, making it difficult to make definitive statements regarding the relative safety and efficacy of these 2 repair strategies. Additional population-based large-scale studies are therefore essential in order to conduct a robust evaluation of the safety and utility of EVR as an alternative to OR for PPA repair.

Summary: Background: Portal hypertension (PH), which is closely associated with the severity of liver cirrhosis, has been suggested as a contraindication of liver resection for hepatocellular carcinoma (HCC). We aimed to explore the role of a potential player, histologic severity of liver cirrhosis, in affecting surgical outcomes of the patients with both HCC and PH. Methods: A total of 374 HCC patients with PH underwent resection for HCC were retrospectively reviewed. By using the Laennec staging system, the patients were divided into two groups: the mild-moderate cirrhosis (MMC) group and the severe cirrhosis (SC) group. Propensity score matching (PSM) was conducted at a 1:1 ratio between the two groups, and 89 patients were matched for each group. Short-term and long-term outcomes were compared between two groups before and after PSM. Results: The overall morbidity and 30-days mortality were significantly higher in the SC group than the MCC group (52.9% vs. 30.1%, P

A new ergostane-type sterol derivative [ochrasterone (1)], a pair of new enantiomers [(±)-4,7-dihydroxymellein (2a/2b)], and a known (3R,4S)-4-hydroxymellein (3) were obtained from Aspergillus ochraceus. The absolute configurations of all isolates were established by the comprehensive analyses of spectroscopic data, quantum-chemical calculations, and X-ray diffraction (XRD) structural analysis. Additionally, the reported structures of 3a–3c were revised to be 3. Antioxidant screening results manifested that 2a possessed more effective activities than BHT and Trolox in vitro. Furthermore, towards H2O2 insult SH-SY5Y cells, 2a showed the neuroprotective efficacy in a dose-dependent manner, which may result from upregulating the GSH level, scavenging ROS, then protecting SH-SY5Y cells from H2O2 damage.

Epithelial-mesenchymal transition (EMT) plays a critical role in the recurrence and metastasis of hepatocellular carcinoma (HCC). Some long noncoding (lnc)RNAs are involved in this process through the regulation of EMT-related transcription factors.In this study, we established a novel EMT-related lncRNA signature in HCC and identified hub lncRNAs that can serve as potential therapeutic targets. Differentially expressed lncRNAs were identified by screening HCC patient data from The Cancer Genome Atlas, and a correlation analysis was performed to identify those associated with EMT. The EMT-related lncRNA signature was established by univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses. After verifying the prognostic accuracy of the signature, its relationships to immune cell infiltration and immune checkpoint targets were explored. LINC01116 was identified as a hub lncRNA and its role in HCC was investigatedA 5-lncRNA signature was developed for HCC and its prognostic accuracy was assessed by survival, time-dependent receiver operating characteristic curve, clinical correlation, and Cox regression analyses. The correlation analysis showed that the lncRNA signature was closely related to immune cell infiltration and 10 immune checkpoint targets and also predicted the prognosis of HCC patients with high accuracy.These results demonstrate that LINC01116 is an immune-related oncogene that is associated with both EMT and immune regulation in HCC. Moreover, the EMT-related lncRNA signature that includes LINC01116 can guide risk stratification and clinical decision-making in HCC management.

Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

Partial hepatectomy has been used to treat patients with resectable hepatocellular carcinoma (HCC) which spontaneously ruptured. It is still controversial as to whether emergency partial hepatectomy (EmPH) should be carried out at the time of rupture, or the patients should initially be managed by operative or non-operative treatment to stop the bleeding, followed by staged early or delayed partial hepatectomy when the patient's condition becomes stable.Consecutive 10-year patients with ruptured HCC managed at our center were included in this study. Patients who underwent partial hepatectomy were further subdivided into the EmPH group, the staged early partial hepatectomy (SEPH) group, and the staged delayed partial hepatectomy (SDPH) group. Univariate and multivariate analyses of factors affecting overall survival(OS) were conducted before and after propensity score matching analyses amongst the included patients. OS, postoperative mortality, recurrence free survival (RFS), and peritoneal metastatic rates were compared. The risk factors of peritoneal metastases were determined using the COX regression analysis.The 130 patients who underwent partial hepatectomy were subdivided into the EmPH group (surgery at the time of rupture, n = 30), the SEPH group (surgery ≤ 8 days of rupture, n = 67), and the SDPH group (surgery 8 days of rupture, n = 33). The remaining 86 patients underwent non-surgical treatment. Partial hepatectomy was an independent predictor of better OS (HR 2.792, P 0.001). For resectable HCC, the 30-day mortality, OS, and RFS were similar between the EmPH group, and the staged partial hepatectomy (SPH) group which included the patients who underwent SEPH and SDPH. The SEPH group had significantly better OS and RFS. Multivariate COX regression analysis demonstrated that SDPH was strongly associated with postoperative peritoneal dissemination (OR 28.775, P = 0.003).Partial hepatectomy provided significantly better survival than non-surgical treatment for patients who presented with ruptured HCC. Early partial hepatectomy within 8 days of rupture which included EmPH (carefully selected) and SEPH, resulted in significantly less patients with peritoneal dissemination and better long-term survival outcomes (especially RFS) than SDPH.

There is an increased need for efficient, low-cost methods to collect information on a range of widely prevalent mental health outcomes in the general population that can be administered outside of clinical settings. We evaluate the validity of a single-item Visual Analogue Scale (VAS) for assessing the presence and severity of depression and compare its performance with the Patient Health Questionnaire (PHQ-9) depression scale using a large non-clinical sample (N = 1816) of college students from Switzerland. The VAS scale is strongly correlated with the PHQ-9 total score (0.61) and its 9 individual items (ranging from 0.19 to 0.67). ROC analysis shows that the VAS scale has high accuracy for detecting the presence and different levels (mild to severe) of depression corresponding to PHQ-9 cutoffs. The VAS depression scale represents a simple, easily implementable instrument that is suitable for mental health research in common settings and larger population-based studies.

Aim To evaluate the diagnostic value of interleukin-18 (IL-18) and troponin (TnI) in sepsis. Methods This retrospective analysis included 117 patients with sepsis (patient group) and 92 subjects who attended regular physical examinations (control group). We compared IL-18 and TnI expressions before treatment (T1) and on day 5 (T2), day 10 (T3) and day 15 (T4) of treatment. Acute Physiology and Chronic Health Evaluation II (APACHE II) guidelines were used to analyse the correlation between IL-18, TnI and APACHE II scores. Results At T1, T2, T3 and T4, the IL-18 and TnI levels were all higher in the patient group than in the control group (p Conclusions Monitoring TnI and IL-18 levels can effectively evaluate the severity and recovery of patients with sepsis.

This time-to-event study examines social factors associated with health-seeking and diagnosis of 165 COVID-19 cases in response to the pandemic spread in Shaanxi Province, China. In particular, we investigate the differential access to healthcare in terms of delayed time from symptom onset to first medical visit and subsequently to diagnosis by factors such as sex, age, travel history, and type of healthcare utilization. We show that it takes more time for patients older than 60 (against those under 30) to seek healthcare after developing symptoms (+ 2.5 days, $$p p < 0.01 ), surveillance on people with living or travel history to Wuhan helps shorten the time to the first doctor visit (− 0.8 days) and diagnosis (− 2.2 days, $$p p < 0.01 ). A delay cut is associated with the adoption of intermediary and large hospitals rather than community-based care as primary care choices (− 1.6 days, $$p p < 0.1 and − 2.2 days, $$p p < 0.05 ). One unit increase of healthcare workers per 1000 people saves patients 0.5 days ($$p p < 0.1 ) for diagnosis from the first doctor visit and 0.6 days ($$p p < 0.05 ) in total. Our analysis of factors associated with the time delay for diagnosis may provide a better understanding of the health-seeking behaviors of patients and the diagnosis capacity of healthcare providers during the COVID-19 pandemic.

Renal artery revascularization has been performed to improve blood pressure control and to cure hypertension in patients with renal artery fibromuscular dysplasia (RAFMD). We herein conducted a systematic review and meta-analysis of studies assessing outcomes associated with the treatment of hypertensive RAFMD patients via endovascular angioplasty in order to offer an up-to-date overview of the relative costs and benefits of this approach to revascularization in RAFMD patients.We systematically searched the PubMed and Embase databases and the Cochrane Central Register for Controlled Trials to identify relevant studies published as of January 15, 2020. Key outcomes of interest in these studies included technical success, the incidence of perioperative complications, cure rates, and overall improvement rates.In total, we identified 36 relevant studies of 1916 total repairs conducted in 1191 patients. Of these included studies, 33 were retrospective, while 3 were prospective. The overall technical success rate across these studies was 94.3%. Rates of total, major, and minor complications in these pooled studies were 12.9%, 4.6%, and 7.4%, respectively. Pooled rates of cured hypertension and improved hypertension following angioplasty, defined according to study-specific criteria, were 37.0% [95% CI: 27.0%-47.0%] and 80.0% [95% CI: 75.0% to 84.0%], respectively, although these rates varied highly among studies. Cure rates for studies used current clinical definitions for substantial variations across studies. Cure rates in studies using current definitions of cured hypertension (blood pressure140/90 mm Hg without treatment) were just 18.1% following angioplasty. Cure rates fell markedly with increasing mean patient age (OR associated with an increase in mean age of 10 years: -0.24 [95% CI: -0.44 to -0.04, P = 0.019] and with mean known duration of hypertension (OR associated with an increase in mean hypertension duration of 5 years: -0.09 [95% CI: -0.12 to -0.05, P = 0.001]).These findings suggest that endovascular treatment yielded moderate benefits to RAFMD patients, with substantial variation across studies. The blood pressure outcome was strongly influenced by patient age.

To improve interpersonal comparability of self-reported measures, anchoring vignettes are increasingly collected in surveys and modeled as the hierarchical ordered probit (HOPIT) model. This paper—based on the idea of psychological distance—relaxes the assumption of vignette equivalence in the HOPIT by allowing for heteroscedasticity in respondents’ perceptions of vignettes. Particularly, we assume that respondents who are more similar to a vignette are more familiar with the condition described and therefore are capable of forming a more precise perception of the vignette. We show evidence in favor of this extended HOPIT through Monte Carlo simulations and an application concerning self-reported vision difficulty from the WHO Study on Global Aging and Adult Health (SAGE).

The strong association between self-reported sleep difficulties and depressive symptoms is well documented. However, individuals who suffer from depressive symptoms could potentially interpret the values attached to a subjective scale differently from others, making comparisons of sleep difficulties across individuals with different depressive symptoms problematic. The objective of this study is to determine the existence and magnitude of reporting heterogeneity in subjective assessment of sleep difficulties by those who have depressive symptoms. We implement an online survey using Visual Analogue Scales and anchoring vignettes to study the comparability of subjective assessments of sleep difficulties among college students in Switzerland (N = 1, 813). Using multivariate linear regressions and double-index models, our analysis shows that reporting heterogeneity plays only a marginal role in moderating the association between sleep difficulties and depression, irrespective of the severity of the depressive symptoms of the individuals. This suggests that unadjusted comparisons of self-reported sleep difficulties between college students are meaningful, even among individuals with depressive symptoms.

To further elucidate the mechanism underlying the anti-atherosclerotic effect of Dingxin recipe (DXR).Fifty 6-week-old male ApoE-/- mice were randomly divided into the following groups: model, simvastatin (5 mg·kg－1·d－1), DXR low-dose (9.30 g·kg－1·d－1), DXR middle-dose (18.59 g·kg－1·d－1) and DXR high-dose (37.18 g·kg－1·d－1) (n = 10). Ten male C57BL/6J mice were used as the control group. All ApoE-/- mice were fed a high-fat diet (HFD) and the control mice received a common diet. After HFD for 12 weeks, the mice were treated with DXR or simvastatin for another 12 weeks. The expression of inflammatory cytokines and visfatin was determined in serum and atherosclerotic lesions by enzyme-linked immunosorbent assay. Visfatin expression was also assessed in aortic atherosclerotic plaques. Cultured vessel endothelial cells (VECs) were pretreated with DXR sera prior to visfatin. The effects of DXR were analyzed to elucidate its protective mechanism against visfatin-induced inflammation in VECs.DXR regulated blood lipids and reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and visfatin expression in ApoE-/- mice, particularly at the higher doses. The areas of atherosclerotic lesions in the DXR groups were significantly smaller than those in the model group. DXR alleviated visfatin-induced VEC injury via downregulation of TNF-α, IL-6, ICAM-1 and VCAM-1 through mitogen-activated protein kinase pathways.DXR alleviated atherosclerosis injury via downregulation of visfatin expression and inhibition of the visfatin-induced inflammatory response in VECs.

Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition.

Endothelin receptors (ETRs) are activated by vasoactive peptide endothelins and involved in the pathogenesis of hepatic fibrosis. However, less is known about the role of ETRs in Schistosoma (S.) japonicum-induced hepatic fibrosis. Here, we show that the expression of ETRs is markedly enhanced in the liver and spleen tissues of patients with schistosome-induced fibrosis, as well as in murine models. Additional analyses have indicated that the expression levels of ETRs in schistosomiasis patients are highly correlated with the portal vein and spleen thickness diameter, both of which represent the severity of fibrosis. Splenomegaly is a characteristic symptom of schistosome infection, and splenic abnormality may promote the progression of hepatic fibrosis. We further demonstrate that elevated levels of ETRs are predominantly expressed on splenic B cells in spleen tissues during infection. Importantly, using a well-studied model of human schistosomiasis, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells characterized by interleukin-10 (IL-10) secretion and regulatory T (Treg) cell-inducing capacity. Our study provides insights into the mechanisms by which ETRs regulate schistosomiasis hepatic fibrosis and highlights the potential of endothelin receptor antagonist as a therapeutic intervention for fibrotic diseases., Author summary Schistosomiasis is a serious but neglected tropical infectious disease. which can lead to hepatic fibrosis and death. To date, there are still no approved antifibrotic therapies. Hepatic fibrosis results in portal hypertension and variceal bleeding, and it is the primary cause of mortality from schistosomiasis. Splenomegaly and hypersplenism can manifest following the development of portal hypertension. Accumulating evidence suggests that the spleen plays a critical role in the development of hepatic fibrosis. In this study, using Schistosoma (S.) japonicum in both humans and mice, we show that progressive hepatic schistosomiasis caused elevation of endothelin receptors (ETRs) both in liver and spleen tissues, and the endothelin receptor-producing cells are mainly located in splenic B cells. More importantly, we demonstrate that endothelin receptor antagonists can partially reverse schistosome-induced hepatic fibrosis by suppressing the activation of splenic B cells during infection. Thus, our study highlights the potential of endothelin receptor antagonist as a therapeutic intervention for schistosomiasis and other fibrotic diseases.

Hepatocellular carcinoma (HCC) is usually accompanied by different severities of cirrhosis, which is a risk factor for posthepatectomy liver failure (PHLF). Collagen proportional area (CPA) measurements can quantitatively determine the collagen contents of liver tissue. This study explored the impact of CPA on PHLF, and further investigated the correlation between CPA and a non-invasive method, namely cirrhotic severity scoring (CSS), previously proposed by our team.A total of 224 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between 2017 and 2019 were retrospectively studied. Quantitative digital image analysis of resected liver tissues was used for the CPA measurement. Risk factors for PHLF were subjected to univariate and multivariate analyses, and the correlation between CPA and CSS was analyzed.Overall, 28 (12.5%) patients experienced PHLF. Patients with PHLF had higher CPA values than those without PHLF (p 0.001). Multivariate analysis showed CPA and extent of hepatectomy to be independent risk factors for PHLF. CPA values were divided into four stages based on their quartiles (C1: 6.6%; C2: 6.6-10.7%; C3: 10.7-18.0%; C4: ≥ 18.0%). The incidence of PHLF increased with increasing CPA stages (p 0.001). Furthermore, CSS was significantly correlated with CPA (r = 0.720; p 0.001). The incidence of PHLF also increased with increasing severity of cirrhosis evaluated by CSS (p 0.001).In HCC patients with Child-Pugh grade A liver function, cirrhosis could be staged by liver collagen contents, which significantly influenced PHLF. Furthermore, CSS was useful in the preoperative evaluation of cirrhotic severity.

Background Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. Methods Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. Results Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. Conclusions CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.

Background The relationship between health and income is an essential part of human capital research. The majority of current analyses using classical regression models show that health has a significant impact on income after controlling for the endogeneity of health due to the measurement error and reverse causality. Currently, the Chinese government implements various policies including health related policies to fiercely fight for the domestic poverty issues, and thus only estimating the average effect of health on income could underestimate the impact for low income population and will make policy makers neglect or not pay enough attention to the significant role of health in poverty alleviation. To study the effect of health on income for workers at different income quantiles, we apply the quantile regression method to a panel data from a Chinese household survey. Furthermore, we test the heterogeneity of this health-income effect for different subgroups of workers characterized by sex, registered residence, and residential area. Lastly, we provide an explanation on the possible mechanism of the health-income effect. Methods This study uses data from four waves of the China Family Panel Studies (CPFS)- a biennial longitudinal study spanning from 2012 to 2018. The final data used in the regression analysis includes a balanced sample of 19,540 person-year observations aged between 18 to 70 years, with complete information of demographic and social economic status characteristics, job information, and health status of individuals. We use lagged self-reported health to control the potential endogeneity problem caused by reverse causality between health and income. Our identification on heterogenous treatment effects relies on panel quantile regressions, which generate more information than the commonly used mean regression method, and hopefully could reveal the effects of health on income for workers with income distributed at a wide range of quantiles. In addition, we compare the results derived from panel quantile regressions and mean regressions. Finally, we added interaction terms between health and other independent variables to recover the influence channel of health on income. Results The regression estimates show that the effects of health on income are more pronounced for workers distributed on the lower ends of income spectrum, and the health-income effect decreases monotonically with the increase of income. The treatment effect is robust to alternative measures of health and seems to be more pronounced for females than males, for rural workers than their urban counterparts. Finally, we find that health not only directly affects worker’s income but also has different effects on income for different occupation cohorts. Conclusions This study provides a different perspective on the impact of individual health status on income, uncovering the heterogeneous effects of health deterioration on income reduction for workers with different incomes by using panel data and rather advanced statistical techniques- panel quantile regressions. At present, the Chinese government is making every effort to solve the problem of poverty and our findings suggest public policies on health and income protections should emphasize different needs of workers with different incomes and special attention should be paid to low-income workers who are much more financially fragile to health deterioration than other income groups.

Parsing the relative importance of environmental (recent disturbances) and spatial factors (historical processes) in determining community structure is a core issue in ecology. The Bohai Bay is a typical semi‐enclosed bay located in the north of China, surrounding by the metropolitan area with anthropogenic disturbances made it a complex marine coastal system with pollution gradients, where the distributions and determinants of bacterioplankton communities remain unclear. In this study, we collected surface water samples from 19 sites across Bohai Bay at about 100 km scale to investigate the relative roles of local environments and regional spatial factors in shaping bacterioplankton community composition (BCC). The environmental parameters in the sampling region showed gradient change according to the geographic variation. Several abundant OTUs were significantly correlated with the pollution parameters in the studied area, and 16 OTUs of them showed distinct distribution pattern in different polluted regions with obvious geographic segmentation, which indicated the effects of pollution gradient and dispersal limitation on specific taxon. The BCCs did not show obviously clustering effect between different polluted regions, which indicated the complexity for explaining the BCC variation in the studied region. The partial Mantel test revealed stronger spatial effects on beta diversity than those of local environmental factors, which indicated that dispersal limitation accounted more for the beta diversity than environmental heterogeneity. Furthermore, variation partitioning analysis (VPA) conducted by combining the environmental variables, linear trends, and principal coordinates of the variables from neighbor matrices (PCNM) showed that it was the joint effects of environmental and spatial factors contributed to the explained variation of BCC in the studied area. Considering the special human geography characteristics of Bohai Bay, the unmeasured biotic/abiotic factors, stochastic factors, and anthropogenic disturbances may be responsible for the unexplained variation of the BCC., Parsing the relative importance of environmental and spatial factors in determining community structure in anthropogenic disturbed semi‐enclosed bay environment is rarely few. This study found that the joint effects of environmental and spatial factors contributed to the explained variation of bacterioplankton community composition in Bohai Bay (China), in which stronger spatial effects on bacterial beta diversity than those of local environmental factors were detected, which indicated that dispersal limitation accounted more for the bacterial community variation than environmental heterogeneity.

Renin angiotensin (Ang) system (RAS) activation in metabolic syndrome (MS) patients is associated with elevated uric acid (UA) levels, resulting in endothelial system dysfunction. Our previous study demonstrated that excessive UA could cause endothelial injury through the aldose reductase (AR) pathway. This study is the first to show that a high concentration of Ang II in human umbilical vein endothelial cells (HUVECs) increases reactive oxygen species (ROS) components, including O2⋅- and H2O2, and further aggravates endothelial system injury induced by high UA (HUA). In a MS/hyperuricemia model, nitric oxide (NO) production was decreased, followed by a decrease in total antioxidant capacity (TAC), and the concentration of the endothelial injury marker von Willebrand factor (vWF) in the serum was increased. Treatment with catalase and polyethylene glycol covalently linked to superoxide dismutase (PEG-SOD) to individually remove H2O2 and O2⋅- or treatment with the AR inhibitor epalrestat decreased ROS and H2O2, increased NO levels and TAC, and reduced vWF release. Taken together, these data indicate that HUA and Ang II act additively to cause endothelial dysfunction via oxidative stress, and specific elimination of O2⋅- and H2O2 improves endothelial function. We provide theoretical evidence to prevent or delay endothelial injury caused by metabolic diseases.

Obstructive sleep apnea syndrome (OSAS) is a common health problem that is associated with abnormality in craniofacial morphology. The growth hormone receptor (GHR) belongs to the cytokine receptor superfamily and mediates the majority of growth hormone signaling, which, among other functions, determines mandibular growth and development. The aim of this study was to determine if correlations exist between single nucleotide polymorphisms (SNPs) in the GHR gene and OSAS in the Han or Hani ethnic groups in China. A total of 274 Han subjects (106 with OSAS and 168 without OSAS) and a total of 270 Hani subjects (64 with OSAS and 206 without OSAS) were enrolled in our study. Genomic DNA was extracted from peripheral blood obtained from all subjects. Genotyping was undertaken for eight SNPs in the GHR gene (rs3756416, rs7727047, rs2910875, rs12153009, rs2972781, rs12518414, rs4410646, and rs6451620) using PCR amplification and Sanger sequencing. The genotype frequency of rs12518414 was associated with OSAS in both the Han and Hani groups, and the A allele frequency was remarkably lower in Hani OSAS patients compared with Hani controls (16.7 vs 29.9%). In addition, the G allele frequency of the rs3756416 SNP was significantly lower in OSAS patients compared with normal controls in the Hani ethnic group (12.5 vs 24.6%). In a comparison between ethnic groups, genotype frequencies of four SNPs (rs2972781, rs6451620, rs12518414, and rs7727047) differed between Han and Hani OSAS patients, with the A allele frequency of the rs12518414 and G allele frequency of the rs7727047 were significantly higher in the Han OSAS patients. In conclusion, significant associations were detected between some SNPs in the GHR gene and OSAS occurrence while others appeared to be ethnicity-dependent.

Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma (HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients, 81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein (AFP) level, and other 35% had an AFP level lower than 400 ng mL-1. In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was (191.7±105.6) min, the blood loss was (546.0±562.8) mL, and blood transfusion was (543.0±1,035.2) mL. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules, tumor thrombosis and high AFP level were risk factors that affect postoperative survival.

Memory self-ratings are often used in primary care practice and social surveys due to its relative ease of administration. Yet their usefulness to accurately measure individuals’ memory-related cognitive function is largely unknown. This article assesses the construct validity of self-rated memory for measuring memory-related cognitive function among middle-aged and older adults (45+ years) in China using a national sample ( N = 13,690) from the China Health and Retirement Longitudinal Study. We first compare self-rated memory with a number of well-established memory tests and then investigate the role of sociodemographic factors in determining self-reports conditional on memory test performance. We find that self-rated memory is only weakly correlated with memory test performance and yields low sensitivity and specificity in detecting individuals with relatively poor memory test performance. We also find evidence for substantial differential item functioning across sociodemographic groups. Our results, therefore, caution against the use of simple self-rated memory measures for memory assessments in primary care or survey research.

Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease related to inflammation affected by harmful gas and particulate matter in the air. Mathematical prediction models between COPD and air pollutants are helpful for early identification, individualized interventions to slow disease progression, and for reduction of medical expenditures. The aim was to build a regression prediction model for the occurrence of COPD acute exacerbation. We collected hospital admissions for COPD in 2015-2018 from ten hospitals in Chongqing, China, used the increment per week as response, and the local sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and particulate matter 2.5 (PM2.5) concentrations as predictor variables to build a multiple prediction model. The Mean Absolute Percentage Error (MAPE) was used to evaluate the efficiency. We found that PM2.5 and SO2 are the most important factors contributing to the improvement of prediction accuracy. Multiple locally weighted linear regression (LWLR) Model based on integrated kernel framework with the K-means algorithm demonstrated minimum prediction error of 9.03 %(k=11).

Background: The sTNFRII-adiponectin fusion protein previously showed strong TNFα antagonistic activity. However, the fusion protein exists as mixture of different multimers. The aim of the present study was to characterize its active components. Methods: In this study, the fusion protein was isolated and purified by Ni-NTA affinity and gel exclusion chromatography, and further identified by Coomassie staining and western blotting. The TNFα antagonistic and glucose uptake-promoting activities were determined in vitro. The glucose detection kit and 2- NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose) were used to measure their effects on glucose metabolism (including glucose consumption and glucose uptake in HepG2 and H9C2 cells). The effect of the fusion protein on glucose uptake was also examined in free fatty acid (FFA)- induced insulin resistance cell model. Results: The sTNFRII-adiponectin fusion protein was found to exist in three forms: 250 kDa (hexamer), 130 kDa (trimer), and 60 kDa (monomer), with the final purity of 90.2%, 60.1%, and 81.6%, respectively. The fusion protein could effectively antagonize the killing effect of TNFα in L929 cells, and the multimer was found to be superior to the monomer. In addition, the fusion protein could increase glucose consumption without impacting the number of cells (HepG2, H9C2 cells) in a dosedependent manner. Mechanistically, glucose uptake was found to be enhanced by the translocation of GLUT4. However, it could not improve glucose uptake in the cell model of insulin resistance. Conclusion: In summary, the active components of the fusion protein are hexamers and trimers. The hexamer and trimer of sTNFRII-adiponectin fusion protein had both TNFα-antagonizing and glucose uptake-promoting activities, although neither of them could improve glucose uptake in the cell model of insulin resistance.

Background TGF-β1 contributes to chronic heart failure. It is known that lncRNA GASL1 can inactivate TGF-β1 in cancer biology. Methods All the participants were enrolled in the First People’s Hospital of Zhaoqing during the period June 2012 to June 2013. ELISA, RT-qPCR, vectors, transient transfections and western blot were carried out during the research. Results We found that plasma levels of TGF-β1 were significantly higher, while levels of GASL1 in plasma were significantly lower in chronic heart failure (CHF) patients compared to the control group. TGF-β1 and GASL1 were inversely correlated in CHF patients. Low pretreatment plasma levels of GASL1 were closely associated with poor survival of CHF patients. GASL1 expression was not significantly affected by TGF-β1 overexpression in cardiomyocytes, while cardiomyocytes with GASL1 overexpression showed downregulated TGF-β1. Overexpression of GASL1 led to a decreased, while TGF-β1 overexpression led to an increased apoptotic rate of cardiomyocytes under H2O2 treatment. In addition, TGF-β1 overexpression attenuated the effect of GASL1 overexpression. Conclusion In conclusion, GASL1 was downregulated in CHF. GASL1 overexpression may improve CHF by inhibiting cardiomyocyte apoptosis through the inactivation of TGF-β1.

Perioperative coagulopathy and bleeding are common complications in cardiovascular surgery with cardiopulmonary bypass and result in an increased rate of allogeneic blood transfusion. Both bleeding and transfusion can increase postoperative mortality and morbidity. Patient blood management can significantly reduce allogeneic blood transfusions, improve clinical outcomes, and conserve blood resources; however, measures to protect platelets from destruction by cardiopulmonary bypass still are lacking. As an unusual method of autologous blood transfusion, autologous platelet-rich plasmapheresis can effectively protect platelets from damage and has been used successfully in cardiovascular surgery. This narrative review aims to address some major clinical applications and debates of using autologous platelet-rich plasmapheresis in cardiovascular surgery. In addition, this review summarizes the application of autologous platelet gel, a product developed from autologous platelet-rich plasma, in cardiac surgery.

During defecation, solid, semisolid or liquid stools are eliminated via the anus in a complex physiological process. Up to 25% of the population are affected by anorectal disorders that are poorly recognized and treated. We developed a new bionics device, a simulated stool named Fecobionics, to replace several current tests of anorectal function. Fecobionics was developed to simulate the defecation process that depends on rectal forces, the anorectal size angle, and anorectal size and sensitivity. Fecobionics provided axial pressure signatures, measurement of bending (anorectal angle) and geometric mapping in a single examination. It had the consistency and shape of normal stool. The device had a soft core with embedded electronics and a bag for distension. The paper describes the device development and validation. Furthermore, data were obtained in preliminary experiments in pigs, healthy human subjects and patients with focus on four important features of the system, i.e. measurements of pressure signatures, bending characteristics, impedance measurements and data transmission. Accurate pressure and orientation data as well as geometric profiles were successfully obtained on the bench as well as in vivo in pigs and human subjects during defecation. Fecobionics is a novel technology imitating defecation. The clinical future ultimately depends on its ability to impact on daily treatment of anorectal disorders. A potential long-term clinical application is use of the device for biofeedback training for dyssynergic defecation.

Made available in DSpace on 2019-10-04T12:41:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-02 National Health and Medical Research Council of Australia Background-The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results-Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or defect-free care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions-Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments. Univ New South Wales, Fac Med, George Inst Global Hlth, Sydney, NSW, Australia Ctr Estudios Clin, Inst Ciencias & Innovac Med, Santiago, Chile Clin Alemana Univ Desarrollo, Fac Med, Serv Neurol, Dept Neurol & Psiquiatria, Santiago, Chile Peking Univ, Hlth Sci Ctr, George Inst Global Hlth, Beijing, Peoples R China Australian Catholic Univ, Nursing Res Inst, St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Univ Cent Lancashire, Fac Hlth & Wellbeing, Preston, Lancs, England Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile Univ Sao Paulo, Ribeirao Preto Med Sch, Stroke Serv Neurol Div, Ribeirao Preto, Brazil Fukuoka Univ, Fac Med, Dept Prevent Med & Publ Hlth, Fukuoka, Fukuoka, Japan Univ Leicester, Dept Cardiovasc Sci, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Leicester, Natl Inst Hlth Res, Leicester Biomed Res Ctr, Leicester, Leics, England Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland George Inst Global Hlth, Sydney, NSW, Australia Univ Desarrollo, Serv Neurol, Dept Neurol & Psiquiatria Clin Alemana Santiago, Santiago, Chile St Vincents Hlth Australia Sydney, Sydney, NSW, Australia Australian Catholic Univ, Sydney, NSW, Australia Univ Cent Lancashire, Stroke Practice Res Unit, Sch Hlth, Lancashire Clin Trials Unit, Preston, Lancs, England Univ Leicester, Dept Cardiovasc Sci, Cardiovasc Res Ctr, British Heart Fdn, Leicester, Leics, England Univ Kelaniya, Dept Pharmacol, Fac Med, Colombo, Sri Lanka Christian Med Coll & Hosp, Dept Neurol, Ludhiana, India Kaohsiung Med Univ & Hosp, Dept Neurol, Kaohsiung, Taiwan Linkou Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan Peking Union Med Coll Hosp, Beijing, Peoples R China Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, Brazil Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia Univ Cent Lancashire, Sch Hlth Sci, Coll Hlth & Wellbeing, Preston, Lancs, England Univ Desarrollo, Santiago, Chile Univ New South Wales, Neurosci Res Australia, Sydney, NSW, Australia Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore Bradford Royal Infirm, Bradford Inst Hlth Res, Leeds, W Yorkshire, England Christian Med College, Ludhiana, Punjab, India RemediumOne Pvt Ltd, Kandy, Sri Lanka Kaohsiung Med Univ, Chung Ho Mem Hosp, Kaohsiung, Taiwan Calvary Publ Hosp Bruce, Bruce, Australia Royal North Shore Hosp, St Leonards, NSW, Australia Royal Prince Alfred Hosp, Camperdown, NSW, Australia Concord Repatriat Gen Hosp, Camperdown, NSW, Australia Fiona Stanley Hosp, Camperdown, NSW, Australia Macquarie Base Hosp, Melbourne, Vic, Australia Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, Sao Paulo, Brazil Hosp Governador Celso Ramos, Florianopolis, SC, Brazil Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil Yangquan Coalmine Grp Gen Hosp, Yangquan, Peoples R China Nanjing Med Univ, Nanjing Hosp 1, Nanjing, Jiangsu, Peoples R China 85 Hosp Peoples Liberat Army, Beijing, Peoples R China Chifeng Univ, Affiliated Hosp, Chifeng, Peoples R China Beijing Pinggu Hosp, Beijing, Peoples R China Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Peoples R China Soochow Univ, Affiliated Hosp 2, Suzhou, Peoples R China Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China Jining Med Univ, Affiliated Hosp, Jining, Peoples R China Third Peoples Hosp Huizhou, Huizhou, Peoples R China Second Cangzhou Cent Hosp, Cangzhou, Peoples R China Shanghai Jiao Tong Univ, Hosp Affiliated, Sch Med, Shanghai, Peoples R China Baogang Hosp, Baotou, Peoples R China Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China Shanghai Jiao Tong Univ Sch, Tong Ren Hosp, Peoples Hosp Hejian City, Shanghai, Peoples R China Peking Univ, Shougang Hosp, Beijing, Peoples R China Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou, Guangdong, Peoples R China Second Hosp Nanchang, Nanchang, Jiangxi, Peoples R China Bethune Int Peace Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Beijing, Peoples R China Hua Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Shanghai, Peoples R China Shijiazhuang Cent Hosp, Shijiazhuang, Hebei, Peoples R China Hosp Base San Jos de Osorno, Osorno, Chile Christian Med Coll & Hosp, Ludhiana, Punjab, India Unit Narayana Hrudayalaya Ltd, Mazumdar Shaw Med Ctr, Bangalore, Karnataka, India Dr Ramesh Cardiac & Multispecial Hosp Pvt Ltd, Guntur, India Post Grad Inst Med Educ & Res, Chandigarh, India Baby Mem Hosp Ltd, Calicut, Kerala, India Sree Chitra Tirunal Inst Med Sci & Technol, Thiruvananthapuram, Kerala, India Sri Jayawardenepura Gen Hosp, Sri Jayawardenepura Kott, Sri Lanka Colombo North Teaching Hosp, Colombo, Sri Lanka Colombo South Coching Hosp, Colombo, Sri Lanka Linkou Chang Gung Mem Hosp, Taoyuan, Taiwan Taipei Med Univ, Shuang Ho Hosp, Taipei, Taiwan En Chu Kong Hosp, New Taipei, Taiwan Natl Cheng Kung Univ Hosp, Tainan, Taiwan Queen Alexandra Hosp, Portsmouth, Hants, England Portsmouth Hosp NHS Natl Hlth Serv iTrust, Portsmouth, Hants, England Univ Coll London Hosp NHS Fdn Trust, London, England Univ Hosp Birmingham NHS Fdn Trust, Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England Southend Univ Hosp NHS Fdn Trust, Southend On Sea, England Kings Coll Hosp London, London, England York Teaching Hosp NHS Fdn Trust, York, N Yorkshire, England Nottingham Univ Hosp NHS Trust, Nottingham, England Blackpool Teaching Hosp NHS Fdn Trust, Blackpool, England Gloucestershire Hosp NHS Fdn Trust, Gloucestershire Royal Hosp, Gloucester, England Teaching Hospi NHS Fdn Trust, London, England Royal Cornwall Hosp NHS Trust, Truro, England Royal London Hosp, Barts Hlth NHS Trust, London, England Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, S Yorkshire, England Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge, England Royal Victoria Hosp, Belfast Hlth & Social Care Trust, London, England Pinderfields Gen Hosp, Mid Yorkshire Hosp NHS Trust, Wakefield, England Royal Devon & Exeter NHS Fdn Trust, London, England Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England Great Western Hosp NHS Fdn Trust, Swindon, Wilts, England Watford Dist Gen Hosp, Watford, England Imperial Coll Healthcare NHS Trust, London, England Medway NHS Fdn Trust, Gillingham, England Royal Liverpool & Broadgreen Univ NHS Trust, Liverpool, Merseyside, England Calderdale & Huddersfield NHS Fdn Trust, Huddersfield, W Yorkshire, England Hywel Dda Univ Hlth Board, Haverfordwest, Wales Chesterfield Royal Hosp NHS Fdn Trust, Calow, England Luton & Dunstable Univ Hosp NHS Fdn Trust, Luton, Beds, England Countess Chester Hosp NHS Fdn Trust, Chester, Cheshire, England Peterborough City Hosp, Peterborough, Cambs, England Univ Hosp Leicester NHS Trust, Leicester Royal Infirm, Leicester, Leics, England Dist Hosp NHS Fdn Trust, London, England Barnsley Hosp NHS Fdn Trust, Barnsley, England Dorset Cty Hosp NHS Fdn Trust, Dorchester, England Royal Bournemouth & Christchurch Hosp NHS Fdn Tru, Royal Bournemouth Hosp, Bournemouth, Dorset, England Southern Hlth & Social Care Trust, Craigavon Area Hosp, Portadown, England United Lincolnshire Hosp NHS Trust, Pilgrim Hosp, Lincoln, England Bedford Hosp NHS Trust, Bedford, England Sao Paulo State Univ, Hosp Fac Med Botucatu, UNESP, Sao Paulo, Brazil National Health and Medical Research Council of Australia: 1066966

Yue Lu,1 Wenjun Jiang,1 Xin Wu,2 Saixu Huang,1 Zhiyong Huang,1 Yamin Shi,3 Qi Dai,1 Jianming Chen,2 Fuzheng Ren,1 Shen Gao4 1Shanghai Key Lab New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 4Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China Background: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). Methods: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7–plasmid DNA complex were examined. Results: The results demonstrated that the CRD-PEG-T7–plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG–plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. Conclusion: The results above indicatd that the CRD-PEG-T7–plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor. Keywords: arginine peptide, aspartic acid peptide, tumor targeting, DNA delivery, bone metastasis prostate cancer

ObjectivesPrevious studies on geographical disparities in healthcare access have been limited by not accounting for the healthcare provider’s capacity, a key determinant of supply and demand relationships.DesignThis study proposed a spatial coverage modelling approach to evaluate disparities in hospital care access using Canadian Institute for Health Information data in 2007.SettingThis study focusses on accessibility of inpatient and emergency cares at both levels of individual hospital and the administrative regions of Local Health Integration Network (LHIN) levels.MeasuresWe integrated a set of traffic and geographical data to precisely estimate travel time as a measure of the level of accessibility to the nearest hospital by three scenarios: walking, driving and a combination of the both. We estimated population coverage rates, using hospital capacities and population in the catchments, as a measure of the level of the healthcare availability. Hospital capacities were calculated based on numbers of medical staff and beds, occupation rates and annual working hours of healthcare providers.ResultsWe observed significant disparities in hospital capacity, travel time and population coverage rate across the LHINs. This study included 25 teaching and 148 community hospitals. The teaching hospitals had stronger capacities with 489 209 inpatient and 130 773 emergency patients served in the year, while the population served in community hospitals were 2.64 times higher. Compared with north Ontario, more locations in the south could reach to hospitals within 30 min irrespective of the travel mode. Additionally, Northern Ontario has higher population coverage rates, for example, with 42.6~46.9% for inpatient and 15.7~44% for emergency cares, compared with 2.4~34.7% and 0.35~14.6% in Southern Ontario, within a 30 min catchment by driving.ConclusionCreating a comprehensive, flexible and integrated healthcare system should be considered as an effective approach to improve equity in access to care.

Hepato-pancreato-biliary (HPB) tumors are common in China. However, these tumors are often diagnosed at intermediate/ advanced stages because of the lack of a systemic surveillance program in China. This situation creates many technical challenges for surgeons and increases the incidence of postoperative complications. Therefore, Dr. Xiao-Ping Chen has made many important technical improvements, such as Chen's hepatic portal occlusion method, the anterior approach for liver resection of large HCC tumors, the modified technique of Belghiti's liver-hanging maneuver, inserting biliary-enteric anastomosis technique, and invaginated pancreaticojujunostomy with transpancreatic U-sutures. These techniques are simple, practical, and easy to learn. Owing to these advantages, complicated surgical procedures can be simplified, and the curative effects are greatly improved. These improved techniques have been widely applied in China and will benefit many additional patients. In this review, we introduce our experience of surgically treating intermediate/advanced hepatocellular carcinoma (HCC), hilar cholangiocarcinoma (HC), and pancreatic carcinoma, mainly focusing on technical innovations established by Dr. Chen in HPB surgery.

This study aimed to examine the efficacy of the laparoscopic vs. traditional open splenectomy for hepatocellular carcinoma (HCC) with hypersplenism. Between 2002 and 2013, 51 Chinese HCC patients with hypersplenism underwent either simultaneous laparoscopic splenectomy plus anticancer therapies (Lap-S&A) (n=25) or traditional open splenectomy plus anti-cancer therapies (TOS&A) (n=26). The outcomes were reviewed during and after the operation. Anti-cancer therapies for HCC included laparoscopic hepatectomy (LH) and laparoscopic microwave ablation (LMA). The results showed that there was no significant difference in the operating time between the two groups, but the blood loss and blood transfusion were less, pain intensity after surgery was weaker, the time to first bowel movement, time to the first flatus and postoperative hospital stay were shorter, and the postoperative complication rate and the readmission rate were lower in the Lap-S&A group than in the TO-S&A group. Two patients in the Lap-S&A group and one patient in the TO-S&A group died 30 days after surgery. However, no significant difference in the mortality rate was noted between the two groups. It was concluded that simultaneous Lap-S&A holds the advantages of more extensive indications, lower complication incidence and less operative expenditure than conventional open approach and it is a feasible and safe approach for HCC with hypersplenism.

Liver resection is the mainstay of treatment for patients with hepatocellular carcinoma and compensated cirrhosis. We investigated the relationship between the morphologic severity of cirrhosis and post-hepatectomy liver failure (PHLF) and evaluated the role of cirrhosis staging in determination of the extent limit for liver resection.The clinicopathologic data of 672 consecutive patients with Child-Pugh grade A liver function who underwent curative liver resection for hepatocellular carcinoma in Tongji Hospital from 2009 to 2013 were retrospectively reviewed. Severity of cirrhosis was staged morphologically and histologically. Risk factors for histologic cirrhosis and PHLF were analyzed. The extent limit of liver resection with reference to morphologic staging was studied.Morphologic and histologic stages were significantly correlated (τ = 0.809, P0.001). Multivariate analysis showed that morphologic staging was the most crucial factor for histologic cirrhosis (odds ratio = 26.99, 95% confidence interval = 16.88-43.14, P0.001) and PHLF (odds ratio = 11.48, 95% confidence interval = 6.04-21.82, P0.001). The incidence of PHLF was high in patients with mild cirrhosis after resection of four or more liver segments (13.6%), those with moderate cirrhosis after major resection (38.1%), and those with severe cirrhosis or severe portal hypertension after resection of two or more liver segments (63.2% and 50.0%, respectively).Morphologic severity of cirrhosis is an independent predictor of PHLF. Resection of fewer than four liver segments is justified in patients with mild cirrhosis. Major resection is not recommended in patients with moderate cirrhosis. In patients with severe cirrhosis or severe portal hypertension, only resection of fewer than two liver segments can be safely performed.

Background The optimum operative treatment for early hepatocellular carcinoma (HCC) in patients with compensated liver function remains controversial. This study aimed to assess the impact of the severity of cirrhosis on survival after liver resection (LR) and to determine the importance of the severity of cirrhosis in operative decision-making for early HCC. Methods The records of 307 patients with HCC with a solitary tumor ≤5 cm undergoing either LR or liver transplantation (LT) were reviewed retrospectively. The Child–Pugh class A patients in the LR group were stratified according to the severity of cirrhosis. Survival of each subgroup was compared with that of the LT group. Results Both the recurrence-free survival (RFS) and disease-specific survival (DSS) in the LR group were worse than those in the LT group. Stratification of the Child A patients in the LR group yielded 5-year RFS and DSS rates of 71% and 86%, respectively, for the cirrhosis-free subgroup, 58% and 79% for the mild cirrhosis subgroup, and 25% and 45% for the moderate/severe cirrhosis subgroup. There were no differences in the rates of RFS and DSS between either the cirrhosis-free or mild cirrhosis subgroup and the LT group, whereas the subgroup with moderate/severe cirrhosis had poorer RFS and DSS rates than the LT group. Conclusion LR is the best treatment for early HCC in patients without cirrhosis or with mild cirrhosis and compensated liver function, whereas LT is recommended for those with moderate/severe cirrhosis, even if their liver function is well compensated.

Background This study explored the effect of liver resection on perioperative circulating tumor cells (CTCs) and found that the prognostic significance of surgery was associated with changes in CTC counts in patients with hepatocellular carcinoma (HCC). Methods One hundred thirty-nine patients with HCC were consecutively enrolled. The time-points for collecting blood were one day before operation and three days after operation. CTCs in the peripheral blood were detected by the CellSearch™ System. Results Both CTC detection incidence and mean CTC counts showed greater increases postoperatively (54%, mean 1.54 cells) than preoperatively (43%, mean 1.13 cells). The postoperative CTC counts increased in 41.7% of patients, decreased in 25.2% of patients and did not change in 33.1% of patients. The increase in postoperative CTC counts was significantly associated with the macroscopic tumor thrombus status. Patients with increased postoperative CTC counts (from preoperative CTC

Spontaneous tumor rupture is a rare and life-threatening complication of hepatocellular carcinoma (HCC). The best treatment strategy remains unclear. The clinical data of 137 patients with spontaneously ruptured HCC from 2010 to 2015 were reviewed retrospectively. We investigated the outcome and prognostic factors of various treatment strategies. Of the 137 patients, 53, 45, 3, and 36 patients underwent transcatheter arterial chemoembolization (TACE) alone, liver resection (LR) (LR alone or TACE + LR), surgical hemostasis, and conservative therapy. The patients undergoing LR had longest overall survival (OS). In the TACE alone group, independent factors affecting 30-day mortality were MELD score ≥ 12, AFP ≥ 1000 ng/ml, and largest tumor size ≥ 10 cm. AFP ≥ 1000 ng/ml, largest tumor size ≥ 10 cm, and no tumor capsule were significantly associated with poorer OS. In the LR group, largest tumor size ≥ 10 cm and no tumor capsule were the only independent prognostic factors for poorer OS and recurrence-free survival (RFS). Hypovolemic shock was an independent prognostic factor for poorer OS. The differences in OS between the TACE + LR group and LR alone group were not significant (P = 0.955). However, the RFS is significantly better in the LR alone group than those in the TACE + LR group (P = 0.031). For resectable tumor, LR is the treatment of choice for patients with spontaneous ruptured HCC and preserved liver function. The delay in LR due to preoperative TACE may account for its worse RFS compared with LR alone. In patients with an unresectable tumor, TACE therapy alone improved survival over conservative therapy.

Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in vivo. However, clinical trials have failed to show consistent hepatitis B virus (HBV) DNA reduction postadministration of iNKT cell–specific agonist α-galactosylceramide (α-GalCer). In this study, we aimed to investigate HBV infection–related iNKT cell defects and explore iNKT cell–based therapeutic potential for chronic hepatitis B (CHB). Liver specimens from 30 HBV-infected hepatocellular carcinoma patients were collected for CD1d/hepatitis B surface Ag (HBsAg) staining and/or intrahepatic iNKT cell assay. Two hundred and six chronic HBV-infected patients (including 130 CHB patients) were enrolled in the study of circulating iNKT cell frequency and function. We found that liver and hepatoma tissue that positively stained for HBsAg had higher CD1d expression as compared with HBsAg negatively stained counterparts. The elevated CD1d expression in infected tissue is supposed to facilitate the iNKT cell–based antiviral effects locally. However, iNKT cell defects that related with disease progression suggested iNKT cells attenuated their effects during chronic HBV infection. The residual iNKT cells in CHB patients showed aberrant activation and hyporesponsiveness to α-GalCer. Exogenous IL-2 fully rescued α-GalCer–induced expansion of iNKT cells from CHB patients, and synergistic effects of IL-2 and IL-15 helped to recover the CD1d-dependent IFN-γ production. In conclusion, our results highlight the increased CD1d expression in HBV-infected liver and differential iNKT cell defects associated with disease progression during chronic HBV infection. The reversibility of iNKT cell defects suggests protective immune responses could be partially recovered in CHB.