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Abstract CD8+ T cell spatial distribution in the context of tumor microenvironment (TME) dictates the immunophenotypes of tumors, comprised of immune-infiltrated, immune-excluded and immune-desert, discriminating “hot” from “cold” tumors. The infiltration of cytotoxic CD8+ T cells is associated with favorable therapeutic response. Hitherto, the immunophenotypes of esophageal squamous cell carcinoma (ESCC) have not yet been comprehensively delineated. Herein, we comprehensively characterized the immunophenotypes of ESCC and identified a subset of ESCC, which was defined as cold tumor and characterized with CD8+ T cell-desert TME. However, the mechanism underlying the defect of CD8+ T cells in TME is still pending. Herein, we uncovered that tumor cell-intrinsic EZH2 with high expression was associated with the immunophenotype of immune-desert tumors. Targeted tumor cell-intrinsic EZH2 rewired the transcriptional activation of CXCL9 mediated by NF-κB and concomitantly reinvigorated DC maturation differentiation via inducing the reduction of VEGFC secretion, thereby enhancing the infiltration of cytotoxic CD8+ T cells into TME and inhibiting tumor immune evasion. Our findings identify EZH2 as a potential therapeutic target and point to avenues for targeted therapy applied to patients with ESCC characterized by CD8+ T cell-desert tumors.

Background: Immune-mediated necrotizing myopathy (IMNM), a subgroup of idiopathic inflammatory myopathies (IIMs), is characterized by severe proximal muscle weakness and prominent necrotic fibers but no infiltration of inflammatory cells. IMNM pathogenesis is unclear. This study investigated key biomarkers and potential pathways for IMNM using high-throughput sequencing and bioinformatics technology. Methods: RNA sequencing was conducted in 18 IMNM patients and 10 controls. A combination of weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis was conducted to identify IMNM-related DEGs. Feature genes were screened out by employing the proteinprotein interaction (PPI) network, support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage selection operator (LASSO). Quantitative real-time polymerase chain reaction (qRTPCR) was performed to verify their differential expression, and the receiver operating characteristic curve (ROC) was used to evaluate their diagnostic efficiency. Functional enrichment analysis was applied to reveal the hidden functions of feature genes. Furthermore, 28 immune cell abundance patterns in IMNM samples were measured. Results: We identified 193 IMNM-related DEGs that were aberrantly upregulated in the IMNM population and were closely associated with immune-inflammatory responses, regulation of skeletal and cardiac muscle contraction, and lipoprotein metabolism. With the help of the PPI network and the LASSO and SVM-RFE algorithms, three feature genes, LTK, MYBPH, and MYL4, were identified and further confirmed by qRTPCR. ROC curves among IMNM, dermatomyositis (DM), inclusion body myositis (IBM), and polymyositis (PM) samples validated the LTK and MYL4 genes as IMNM-specific feature markers. In addition, all three genes had a notable association with the autophagylysosome pathway and immune-inflammatory responses. Ultimately, IMNM displayed a marked immune-cell infiltrative microenvironment. The most significant correlation was found between CD4 T cells, CD8 T cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs). Conclusions: LTK, MYBPH, and MYL4 were identified as potential key molecules for IMNM and are believed to play a role in the autophagylysosome pathway and muscle inflammation.

Abstract Background Lung cancer (LC) is one of the most common cancers and a leading cause of cancer‐related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. Methods LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH‐DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co‐IP was performed to assess the interaction between ITCH and TXNIP. Results ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin‐interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain‐of‐function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia‐conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia‐induced features in LC cells with ITCH C830A was found to be similar. Conclusion Our results suggest a novel mechanism underlying the changes in ITCH‐mediated malignant phenotypes of hypoxia‐conditioned LC cells via TXNIP.

BackgroundInclusion body myositis (IBM) is a slowly progressive inflammatory myopathy that typically affects the quadriceps and finger flexors. Sjögren’s syndrome (SS), an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands has been reported to share common genetic and autoimmune pathways with IBM. However, the exact mechanism underlying their commonality remains unclear. In this study, we investigated the common pathological mechanisms involved in both SS and IBM using a bioinformatic approach.MethodsIBM and SS gene expression profiles were obtained from the Gene Expression Omnibus (GEO). SS and IBM coexpression modules were identified using weighted gene coexpression network analysis (WGCNA), and differentially expressed gene (DEG) analysis was applied to identify their shared DEGs. The hidden biological pathways were revealed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, protein−protein interaction (PPI) networks, cluster analyses, and hub shared gene identification were conducted. The expression of hub genes was validated by reverse transcription quantitative polymerase chain reaction (RT−qPCR). We then analyzed immune cell abundance patterns in SS and IBM using single-sample gene set enrichment analysis (ssGSEA) and investigated their association with hub genes. Finally, NetworkAnalyst was used to construct a common transcription factor (TF)-gene network.ResultsUsing WGCNA, we found that 172 intersecting genes were closely related to viral infection and antigen processing/presentation. Based on DEG analysis, 29 shared genes were found to be upregulated and enriched in similar biological pathways. By intersecting the top 20 potential hub genes from the WGCNA and DEG sets, three shared hub genes (PSMB9, CD74, and HLA-F) were derived and validated to be active transcripts, which all exhibited diagnostic values for SS and IBM. Furthermore, ssGSEA showed similar infiltration profiles in IBM and SS, and the hub genes were positively correlated with the abundance of immune cells. Ultimately, two TFs (HDGF and WRNIP1) were identified as possible key TFs.ConclusionOur study identified that IBM shares common immunologic and transcriptional pathways with SS, such as viral infection and antigen processing/presentation. Furthermore, both IBM and SS have almost identical immune infiltration microenvironments, indicating similar immune responses may contribute to their association.

BackgroundDysferlinopathy refers to a group of muscle diseases with progressive muscle weakness and atrophy caused by pathogenic mutations of the DYSF gene. The pathogenesis remains unknown, and currently no specific treatment is available to alter the disease progression. This research aims to investigate important biomarkers and their latent biological pathways participating in dysferlinopathy and reveal the association with immune cell infiltration.MethodsGSE3307 and GSE109178 were obtained from the Gene Expression Omnibus (GEO) database. Based on weighted gene co-expression network analysis (WGCNA) and differential expression analysis, coupled with least absolute shrinkage and selection operator (LASSO), the key genes for dysferlinopathy were identified. Functional enrichment analysis Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to disclose the hidden biological pathways. Following that, the key genes were approved for diagnostic accuracy of dysferlinopathy based on another dataset GSE109178, and quantitative real-time polymerase chain reaction (qRT-PCR) were executed to confirm their expression. Furthermore, the 28 immune cell abundance patterns in dysferlinopathy were determined with single-sample GSEA (ssGSEA).Results1,579 differentially expressed genes (DEGs) were screened out. Based on WGCNA, three co-expression modules were obtained, with the MEskyblue module most strongly correlated with dysferlinopathy. 44 intersecting genes were recognized from the DEGs and the MEskyblue module. The six key genes MVP, GRN, ERP29, RNF128, NFYB and KPNA3 were discovered through LASSO analysis and experimentally verified later. In a receiver operating characteristic analysis (ROC) curve, the six hub genes were shown to be highly valuable for diagnostic purposes. Furthermore, functional enrichment analysis highlighted that these genes were enriched mainly along the ubiquitin-proteasome pathway (UPP). Ultimately, ssGSEA showed a significant immune-cell infiltrative microenvironment in dysferlinopathy patients, especially T cell, macrophage, and activated dendritic cell (DC).ConclusionSix key genes are identified in dysferlinopathy with a bioinformatic approach used for the first time. The key genes are believed to be involved in protein degradation pathways and the activation of muscular inflammation. And several immune cells, such as T cell, macrophage and DC, are considered to be implicated in the progression of dysferlinopathy.

BackgroundHypertrophic cardiomyopathy (HCM) is the prevalent inherited cardiomyopathy and a major contributor to sudden death and heart failure in young adults. Although depression has been associated with poor prognosis in patients with cardiovascular disease, the relationship between anxiety and HCM clinical outcomes has not been addressed. We aimed to determine the prevalence of anxiety symptoms in patients with HCM and the association between anxiety and adverse prognosis in this population.MethodsA total of 793 patients with HCM were prospectively enrolled and followed up for a mean of 4.1 years from March 2014 to January 2018. The primary endpoint was sudden cardiac death (SCD) events, and the secondary endpoint was HCM-related heart failure events. Anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) during outpatient visits or hospital stays.ResultsElevated scores on the HADS anxiety subscale (HADS-A ≥ 8) were defined as clinically significant anxiety. SCD and HCM-related heart failure events occurred in 76 and 149 patients, respectively, during the follow-up period. Kaplan–Meier survival curves demonstrated the significant association of anxiety with SCD events (log-rank P = 0.012) and HCM-related heart failure events (log-rank P = 0.001). Multivariable Cox regression analysis showed anxiety as a predictor of SCD events and HCM-related heart failure events (adjusted hazard ratio [HR] = 1.42, 95% confidence interval [CI] = 1.12–2.04, P = 0.03; adjusted HR = 2.9,2 95% CI = 1.73–4.03, P < 0.001), independent of conventional risk factors and depression. Besides, patients with comorbid anxiety and depression showed a fourfold higher risk of heart failure events and 3.5-fold higher risk of SCD versus those with neither (adjusted HR = 4.08, 95% CI = 2.76–5.91, P < 0.001; adjusted HR = 3.52, 95% CI = 2.24–4.67, P < 0.001, respectively).ConclusionsAnxiety was prevalent among Chinese patients with HCM, and it was independently associated with a higher risk of SCD and HCM-related heart failure events, particularly when comorbid with depression. Psychological assessment and intervention should be considered to alleviate anxiety symptoms in this population.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier: ChiCTR2000040759.

Holmium laser lithotripsy (HLL) is one of the common surgical methods for urolithiasis. It causes minor surgical trauma, but complications are not rare. Extracorporeal membrane oxygenation (ECMO) treatment of sepsis is common, but venoarterial (VA)-ECMO treatment of urosepsis has not been reported yet. In this article, we reported a 67-year-old female patient with refractory septic shock caused by HLL under percutaneous nephroscope, involving breathing, heart, kidney and other organs, and organs support treatment was ineffective for the patient. Finally, we successfully treated the patient under VA-ECMO with continuous renal replacement therapy (CRRT). Combined ECMO and CRRT may provide a solution for addressing refractory sepsis. Here we present the case and review relevant literature, so as to provide a treatment strategy for patients with refractory urogenic sepsis and to reduce the mortality rate.

The contact resistance between the armature and rails is an important indicator of the contact characteristics in electromagnetic launches. As the contact resistance depends not only on the contact state but also on the contact stress and temperature, there are some limitations in analyzing the contact characteristics using only the contact resistance. In this paper, the contact characteristics of the augmented railgun are analyzed by the combination of contact resistance and sliding friction coefficient. Firstly, the theoretical calculation model of the contact resistance and friction coefficient of the augmented electromagnetic railgun is established. Then the contact resistance and friction coefficient are calculated by the measured values of the muzzle voltage, rail current and armature displacement. Finally, the contact characteristics are analyzed according to the features of the waveforms of the contact resistance and the friction coefficient, and the analysis conclusions are verified by experimental rail images. The results showed that: the aluminum melt film gradually formed on the contact surface reduces the contact resistance and the friction coefficient; the wear and erosion of the armature cause deterioration of the contact state; after the transition, the reliability of the sliding contact between the armature and rails decreases, resulting in an increase in contact resistance.

BackgroundA pocket hematoma is a well-recognized complication that occurs after pacemaker or defibrillator implantation. It is associated with increased pocket infection and hospital stay. Patients suffering from atrial fibrillation and undergoing cardiovascular electronic implantable device (CIED) surgery are widely prescribed and treated with direct oral anticoagulants (DOACs). In this study, the use of a novel compression device was evaluated to examine its ability to decrease the incidence of pocket hematomas following device implantation with uninterrupted DOACs.MethodsA total of 204 participants who received DOACs and underwent CIED implantation were randomized into an experimental group (novel compression device) and a control group (elastic adhesive tape with a sandbag). The primary outcome was pocket hematoma, and the secondary outcomes were skin erosions and patient comfort score. Grade 3 hematoma was defined as a hematoma that required anticoagulation therapy interruption, re-operation, or prolonged hospital stay.ResultsThe baseline characteristics of both groups had no significant differences. The incidence of grades 1 and 2 hematomas was significantly lower in the compression device group than in the conventional pressure dressing group (7.8 vs. 23.5 and 2.0 vs. 5.9%, respectively; P < 0.01). Grade 3 hematoma occurred in 2 of 102 patients in the experimental group and 7 of 102 patients in the control group (2.0 vs. 6.9%; P = 0.03). The incidence rates of skin erosion were significantly lower, and the patient comfort score was much higher in the compression device group than in the control group (P < 0.01). Multivariable logistic regression analysis showed that the use of novel compression device was a significant protective factor for pocket hematoma (OR = 0.42; 95% CI, 0.29–0.69, P = 0.01).ConclusionsThe incidence of pocket hematomas and skin erosions significantly decreases when the proposed compression device is used for patients undergoing device implantation with uninterrupted DOACs. Thus, the length of hospital stay and re-operation rate can be reduced, and patient comfort can be improved.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier: ChiCTR2100049430.

BackgroundMyocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with varying underlying etiologies and occurs in ~5–10% of patients with acute myocardial infarction. Sleep disorders and short sleep duration are common phenomena experienced by patients with coronary heart disease and are associated with poor clinical outcomes. However, the association between sleep quality, sleep duration, and the MINOCA prognosis is less clear.MethodsWe performed a prospective observational study of 607 patients with MINOCA between February 2016 and June 2018. The mean follow-up period was 3.9 years. Sleep quality and sleep duration were measured by the Chinese version of the Pittsburgh Sleep Quality Index. The primary endpoint was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, stroke and heart failure hospitalization.ResultsDuring the follow-up period, all-cause death occurred in 69 participants and 105 participants developed MACE. The Kaplan–Meier survival analysis demonstrated a significant association between poor sleep quality and all-cause mortality (log-rank P = 0.005) and MACE (log-rank P = 0.004). Multivariable Cox regression model indicated that poor sleep quality was an independent predictor of all-cause mortality as well as MACE [adjusted hazard ratio (HR) = 1.649; 95% confidence interval (CI), 1.124–2.790; P < 0.001; and adjusted HR = 1.432; 95% CI, 1.043–2.004; P = 0.003, respectively]. For sleep duration, short sleep duration (8 h/d). A poorer sleep profile (including poor sleep quality and short sleep duration) was associated with a 149.4% increased risk of death (HR = 2.494; 95% CI, 1.754–4.562; P < 0.001) and a 96.7% increased risk of MACE (HR = 1.967; 95% CI, 1.442–3.639; P < 0.001) than those with neither.ConclusionSleep disorders were common among Chinese patients with MINOCA. Poor sleep quality and short sleep duration were independently associated with an increased risk of all-cause mortality and MACE in the MINOCA population. Meanwhile, a poor sleep profile has an additive effect with regard to cardiovascular risks; in these populations, efforts should be made to improve both sleep quality and sleep duration for secondary cardiovascular prevention.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier: ChiCTR2000040701.

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period.Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids.Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was −7.0 [0.6] kg vs. −6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was −7 [0.7] mmHg vs. −7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was −6 [0.5] mmHg vs. −5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial.Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000040468.

Background Hypertrophic cardiomyopathy (HCM) is considered to be the most common cause of sudden death in young people and is associated with an elevated risk of mood disorders. Depression has emerged as a critical risk factor for development and progression of coronary artery disease; however, the association between depression and HCM outcomes is less clear. We sought to examine the impact of depression on clinical outcomes in patients with HCM. Methods and Results Between January 2014 and December 2017, 820 patients with HCM were recruited and followed for an average of 4.2 years. End points were defined as sudden cardiac death (SCD) events and HCM‐related heart failure events. A Chinese version of the Structured Clinical Interview followed the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and was used to diagnose depression. During the follow‐up period, SCD events occurred in 75 individuals (21.8 per 1000 person‐years), and HCM‐related heart failure events developed in 149 individuals (43.3 per 1000 person‐years). Kaplan–Meier cumulative incidence curves showed a significant association of depression disorders with SCD events (log‐rank P=0.001) and HCM‐related heart failure events (log‐rank P=0.005). A multivariate Cox regression analysis indicated that depression was an independent predictor of SCD events and HCM‐related heart failure events (41.9 versus 21.7 per 1000 person‐years; adjusted hazard ratio [HR], 1.9; 95% CI, 1.6–2.3; P

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5–10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA.Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke.Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan–Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286–2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201–2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications.Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

DOI: 10.3969/j.issn.1672-6731.2016.05.001

For dynamic reliability design of complex structures with multiple components, an improved weighted regression distributed collaborative surrogate model method (IWRDCSMM) is developed from the extremum response surface method (ERSM), decomposed-coordinated thought, and improved weighted regression principle. The ERSM is used to address the dynamic reliability and sensitivity analyses of multicomponent structures and enhance the computing efficiency. The decomposed-coordinated thought is applied to handle the relationship among multiple components. The improved weighted regression method is used to find the efficient samples with smaller errors to improve the modeling accuracy. The proposed method is first introduced for dynamic probabilistic analysis (including reliability analysis and sensitivity analysis) of multicomponent structures. The method is then mathematically modeled by adopting the efficient samples selected based on the improved weighted regression method. Finally, the radial deformation dynamic probabilistic analysis of an aeroengine turbine blisk assembled by blade and disk is accomplished, in respect of the IWRDCSMM, fluid-thermal-structure interaction, and the randomness of input parameters within the time domain [0, T]. The results illustrate that the reliability degree of turbine blisk radial deformation is 0.9951 when the allowable value uallow is 2.30 × 10−3 m, and all the input parameters affecting the turbine blisk radial deformation are gas temperature, angular speed, inlet velocity, outlet pressure, material density, and inlet pressure, successively. As revealed by the comparison of different methods, the IWRDCSMM has high fitting speed and simulation efficiency with the guarantee of accuracy. The efforts of this study provide a promising dynamic probabilistic analysis technique for complex structures with multiple components and enrich mechanical reliability theory.

Background: Stroke volume variation (SVV) has been shown to be a reliable predictor of fluid responsiveness. However, the predictive role of SVV measured by FloTrac/Vigileo system in prediction of fluid responsiveness was unproven in patients undergoing ventilation with low tidal volume. Methods: Fifty patients undergoing elective gastrointestinal surgery were randomly divided into two groups: Group C [n1=20, tidal volume (Vt) = 8 ml/kg, frequency (F) = 12/min] and Group L [n2=30, Vt= 6 ml/kg, F=16/min]. After anesthesia induction, 6% hydroxyethyl starch130/0.4 solution (7 ml/kg) was intravenously transfused. Besides standard haemodynamic monitoring, SVV, cardiac output, cardiac index (CI), stroke volume (SV), stroke volume index (SVI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI) were determined with the FloTrac/Vigileo system before and after fluid loading. Results: After fluid loading, the MAP, CVP, SVI and CI increased significantly, whereas the SVV and SVR decreased markedly in both groups. SVI was significantly correlated to the SVV, CVP but not the HR, MAP and SVR. SVI was significantly correlated to the SVV before fluid loading (Group C: r = 0.909; Group L: r = 0.758) but not the HR, MAP, CVP and SVR before fluid loading. The largest area under the ROC curve (AUC) was found for SVV (Group C, 0.852; Group L, 0.814), and the AUC for other preloading indices in two groups ranged from 0.324 to 0.460. Conclusion: SVV measured by FloTrac/Vigileo system can predict fluid responsiveness in patients undergoing ventilation with low tidal volumes during gastrointestinal surgery.

Icariin (ICA) is a major flavonoid that contains the active compound Epimedii Folium. However, ICA’s pharmacokinetic characteristics remain unsatisfactory due to its low bioavailability, and hence limited drugability. In order to improve its pharmacokinetics and achieve prolonged blood circulation time, a novel polymeric micelle, made of the self-assembled micelle between poly (ethylene glycol)-poly (L-lactic acid) (PEG-PLLA) and poly (D-lactic acid)-poly(N-isopropylacrylamide) (PDLA-PNIPAM), was designed to encapsulate ICA. Our experimental results showed that this polymeric micelle formulation of ICA exhibited uniform nano-size distribution and high stability within 48 h. The new formulation also allowed sustained ICA release in an in vitro drug release study. Furthermore, in vivo experiments revealed that ICA bioavailability in the PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation was significantly higher compared to ICA alone, or ICA in the traditional Pluronic F127 micelle formulation. Finally, we show that metabolite analysis confirmed that ICA within the PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation provided better drug protection, reduced drug metabolites production, and decreased undesired first-pass effects. Overall, these data show that ICA within PEG-PLLA/PDLA-PNIPAM polymeric micelle formulation exhibit advantages, in terms of improved physicochemical properties, sustained release of ICA in vitro, and improved bioavailability of ICA in vivo, which represent a feasible approach for improving the drugability of pharmaceutical small molecules with low bioavailability or poor stability.

OBJECTIVE: To examine the difference between schizophrenia patients and normal controls on velocity and acceleration of saccade, by using the basic visually guided saccade (VGS) paradigm. METHODS: Eighteen schizophrenia outpatients and fourteen normal controls participated in the VGS task. Multiple indicators, including amplitude, duration, velocity, latency, accuracy rate, acceleration, and deceleration were analyzed. Asymmetric acceleration index (AAI) was introduced to describe the difference between peak acceleration and peak deceleration. The correlation coefficient (RAD) of AAI and duration was computed to examine the difference between schizophrenia patients and normal controls. RESULTS: No significant difference between patients and normal controls was found on amplitude, duration, latency, and accuracy rate. However, RAD values of schizophrenia patients were significantly lower than the control group. CONCLUSION: Compared to normal controls, association of saccade duration and saccade acceleration/deceleration asymmetry during visually guided saccade was lower in schizophrenia patients.

Isolated from Annona squamosa L, Annonaceous acetogenins (ACGs) exhibit a broad range of biological properties yet absorbed badly due to the low solubility. Solid dispersion in polyethylene glycol 4000 (PEG 4000) has been developed to increase the solubility and oral absorption of ACGs. The formulation of ACGS-solid dispersion was optimized by a simplex lattice experiment design and carried out by a solvent-fusion method. We studied the absorption property of ACGs in rat’s intestine, which showed there was a good absorption and uptake percentages with solid dispersion. The study on uptake percentage in different regions of rat’s intestine attested that the duodenum had the best permeability, followed by jejunum, ileum, and colon in order with no significant differences. So the paper drew the conclusion that solid dispersion could improve the solubility and oral absorption of annonaceous acetogenins.

Corn hulls were abundant and inexpensive byproducts of the corn dry or wet milling processes, but most of them were discarded as agro-wastes. The aim of this study was to extract the dietary fiber by hot-compressed water (HCW) from defatted corn hull and to determine the chemical properties. Results showed that temperature and time played critical roles in extraction efficiency; the maximal yield of dietary fiber A (DFA) extracted by HCW reached 33.0% at 150°C for 60 min. The yield of dietary fiber B (DFB) increased from 2.0% to 56.9% as the temperature increased from 110 to 180°C, while the yield of solid residue (SR) decreased from 88.7% to 27.7%. Fourier transform infrared spectroscopy (FT-IR) results demonstrated that C-H, O-H, C=O, COO- occurred in the DFA, SR and DFB. The dietary fiber polysaccharides consisted of arabinose, galactose, glucose, xylose and uronic acid. [ABSTRACT FROM AUTHOR]

Associations of multimorbidity and income with hospital admission were investigated in population samples from 3 widely differing health care systems: Scotland (n = 36,921), China (n = 162,464), and Hong Kong (n = 29,187). Multimorbidity increased odds of admissions in all 3 settings. In Scotland, poorer people were more likely to be admitted (adjusted odds ratio [aOR] = 1.62; 95% CI, 1.41-1.86 for the lowest income group vs the highest), whereas China showed the opposite (aOR = 0.58; 95% CI, 0.56-0.60). In Hong Kong, poorer people were more likely to be admitted to public hospitals (aOR = 1.68; 95% CI, 1.36- 2.07), but less likely to be admitted to private ones (aOR = 0.18; 95% CI, 0.13- 0.25). Strategies to improve equitable health care should consider the impact of socioeconomic deprivation on the use of health care resources, particularly among populations with prevalent multimorbidity. [ABSTRACT FROM AUTHOR]

Background China, like other countries, is facing a growing burden of chronic disease but the prevalence of multimorbidity and implications for the healthcare system have been little researched. We examined the epidemiology of multimorbidity in southern China in a large representative sample. The effects of multimorbidity and other factors on usual source of healthcare were also examined. Methods We conducted a large cross-sectional survey among approximately 5% (N =162,464) of the resident population in three prefectures in Guangdong province, southern China in 2011. A multistage, stratified random sampling was adopted. The study population had many similar characteristics to the national census population. Interviewer-administered questionnaires were used to collect self-report data on demographics, socio-economics, lifestyles, healthcare use, and health characteristics from paper-based medical reports. Results More than one in ten of the total study population (11.1%, 95% confidence interval (CI) 10.6 to 11.6) had two or more chronic conditions from a selection of 40 morbidities. The prevalence of multimorbidity increased with age (adjusted odds ratio (aOR) =1.36, 95%CI 1.35 to 1.38 per five years). Female gender (aOR =1.70, 95%CI 1.64 to 1.76), low education (aOR =1.26, 95%CI 1.23 to 1.29), lack of medical insurance (aOR =1.79, 95%CI 1.71 to 1.89), and unhealthy lifestyle behaviours were independent predictors of multimorbidity. Multimorbidity was associated with the regular use of secondary outpatient care in preference to primary care. Conclusions Multimorbidity is now common in China. The reported preferential use of secondary care over primary care by patients with multimorbidity has many major implications. There is an urgent need to further develop a strong and equitable primary care system. [ABSTRACT FROM AUTHOR]

In this paper, we analyze a class of new generalized Emden-Fowler equations. By using the generalized Riccati transformation and specific analytical skills, new oscillation criteria are obtained which generalize and improve some known results. [ABSTRACT FROM AUTHOR]

Background: The clinical application of cantharidin (CA) is limited by its insolubility, toxicity and short half-life in circulation. This study aims to achieve a steady and sustained blood concentration-time profile, using solid lipid nanoparticles (SLNs) as a drug carrier. Methods: CA-SLNs were prepared by a film dispersion-ultrasonication method. The physiochemical properties were studied by transmission electron microscopy. In vitro release and in vivo evaluation of CA-SLNs were studied by GC and GC-MS, while a comparison of the pharmacokinetic properties between CA-SLNs and free CA was performed in rats. Results: The mean size, drug content and encapsulation yield of CA-SLNs were 121 nm, 13.28 ± 0.12% and 93.83 ± 0.45%, respectively. The results show that CA-SLNs had a sustained release profile without a burst effect, a higher bioavailability than free CA after oral administration, and that the relative bioavailability of CA-SLNs to free CA was 250.8%. Conclusion: CA-SLNs could improve the solubility and oral bioavailability of CA. [ABSTRACT FROM AUTHOR]

The article presents a pharmacokinetic study on the determination of plasma concentration of cantharidin (CA) after a clinic dose in beagle dogs with the use of mass spectrometry and gas chromatography. It states that cantharidin was used in China as a cancer prevention drug wherein clinicians proved it therapeutic efficacy. Moreover, it found out that hydrochloric acid precipitation is effective for identifying the level of cantharidin plasma concentration.