Radiation pneumonia predictive model for radiotherapy in esophageal carcinoma patients.

BACKGROUND: The machine learning models with dose factors and the deep learning models with dose distribution matrix have been used to building lung toxics models for radiotherapy and achieve promising results. However, few studies have integrated clinical features into deep learning models. This study aimed to explore the role of three-dimension dose distribution and clinical features in predicting radiation pneumonitis (RP) in esophageal cancer patients after radiotherapy and designed a new hybrid deep learning network to predict the incidence of RP. METHODS: A total of 105 esophageal cancer patients previously treated with radiotherapy were enrolled in this study. The three-dimension (3D) dose distributions within the lung were extracted from the treatment planning system, converted into 3D matrixes and used as inputs to predict RP with ResNet. In total, 15 clinical factors were normalized and converted into one-dimension (1D) matrixes. A new prediction model (HybridNet) was then built based on a hybrid deep learning network, which combined 3D ResNet18 and 1D convolution layers. Machine learning-based prediction models, which use the traditional dosiomic factors with and without the clinical factors as inputs, were also constructed and their predictive performance compared with that of HybridNet using tenfold cross validation. Accuracy and area under the receiver operator characteristic curve (AUC) were used to evaluate the model effect. DeLong test was used to compare the prediction results of the models. RESULTS: The deep learning-based model achieved superior prediction results compared with machine learning-based models. ResNet performed best in the group that only considered dose factors (accuracy, 0.78 ± 0.05; AUC, 0.82 ± 0.25), whereas HybridNet performed best in the group that considered both dose factors and clinical factors (accuracy, 0.85 ± 0.13; AUC, 0.91 ± 0.09). HybridNet had higher accuracy than that of Resnet (p = 0.009). CONCLUSION: Based on prediction results, the proposed HybridNet model could predict RP in esophageal cancer patients after radiotherapy with significantly higher accuracy, suggesting its potential as a useful tool for clinical decision-making. This study demonstrated that the information in dose distribution is worth further exploration, and combining multiple types of features contributes to predict radiotherapy response.

Analysis of the risk factors of radiation pneumonitis and the predictive ability of dosiomics in non-small-cell lung cancer.

Purpose: This prospective study investigated the incidence of radiation pneumonitis (RP) after immunotherapy followed by radiotherapy in non-small-cell lung cancer, analyzed the risk factors for RP, and explored the predictive performance of dosimetry and dosiomics. Methods & materials: Risk factors for grade ≥2 RP were calculated by using a logistic regression model. Predictive performance was compared on the basis of area under the curve values. Results: Grade ≥2 RP occurred in 16 cases (26.7%). The AUC values of V5 Gy, gray-level dependence matrix-small dependence high gray-level emphasis (GLDM-SDHGLE) and combined features were 0.685, 0.724 and 0.734, respectively. Conclusion: Smoking history, bilateral lung V5 Gy and GLDM-SDHGLE were independent risk factors for RP. Dosiomics can effectively predict RP.

GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma.

Background: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma. Methods: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers. Results: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid. Conclusions: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.

An intravenous anesthetic drug-propofol, influences the biological characteristics of malignant tumors and reshapes the tumor microenvironment: A narrative literature review.

Malignant tumors are the second leading cause of death worldwide. This is a public health concern that negatively impacts human health and poses a threat to the safety of life. Although there are several treatment approaches for malignant tumors, surgical resection remains the primary and direct treatment for malignant solid tumors. Anesthesia is an integral part of the operation process. Different anesthesia techniques and drugs have different effects on the operation and the postoperative prognosis. Propofol is an intravenous anesthetic that is commonly used in surgery. A substantial number of studies have shown that propofol participates in the pathophysiological process related to malignant tumors and affects the occurrence and development of malignant tumors, including anti-tumor effect, pro-tumor effect, and regulation of drug resistance. Propofol can also reshape the tumor microenvironment, including anti-angiogenesis, regulation of immunity, reduction of inflammation and remodeling of the extracellular matrix. Furthermore, most clinical studies have also indicated that propofol may contribute to a better postoperative outcome in some malignant tumor surgeries. Therefore, the author reviewed the chemical properties, pharmacokinetics, clinical application and limitations, mechanism of influencing the biological characteristics of malignant tumors and reshaping the tumor microenvironment, studies of propofol in animal tumor models and its relationship with postoperative prognosis of propofol in combination with the relevant literature in recent years, to lay a foundation for further study on the correlation between propofol and malignant tumor and provide theoretical guidance for the selection of anesthetics in malignant tumor surgery.

Cytotoxic Sesquiterpenoids from Atractylodes chinensis (DC.) Koidz.

Four new sesquiterpenoids named atrchiterpenes A-D (1-4), a new natural product (5), and twelve known compounds (6-17) were isolated from Atractylodes chinensis (DC.) Koidz. Compound 1 was a rare N-containing eudesmane-type sesquiterpenoid. Structure elucidation was performed by spectroscopic techniques, including 1D, 2D NMR spectra, and HR-ESI-MS. Compounds 6-11, 14, and 17 were reported from Atractylodes for the first time. All the isolated compounds were evaluated for cytotoxicity activity. Compound 16 showed moderate cytotoxicity against HepG2 cells with an IC50 value of 5.81±0.47.

Increased levels of serum adenosine deaminase and increased risk of diabetic peripheral neuropathy in type 2 diabetes.

Background: Increased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods: This study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected. Results: A total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency (ß=0.263, t=5.273, p<0.001) and decreases in composite Z score of amplitude (ß=-0.126, t=-2.352, p=0.019) and NCV (ß=-0.201, t=-3.841, p<0.001) after adjusting for other clinical covariates. Moreover, each 5 U/L increase in serum ADA levels was associated with a 1.781-fold increased adjusted odds ratio of having DPN (95% confidence interval: 1.271-2.495). Furthermore, the optimal cut-off value of serum ADA levels to discriminate DPN was ≥14.2 U/L (sensitivity=59.57%, specificity=75.52% and Youden index=0.351) after analysis by receiver operating characteristic curve. Conclusions: Increased serum ADA levels may be a potential risk factor for DPN in patients with T2D.

High-normal serum carcinoembryonic antigen levels and increased risk of diabetic peripheral neuropathy in type 2 diabetes.

BACKGROUND: Increased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). METHODS: All subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN. RESULTS: We ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (ß = 0.132, t = 2.330, p = 0.021), amplitude (ß = - 0.164, t = - 2.838, p = 0.005) and NCV (ß = - 0.210, t = - 3.662, p < 0.001). Moreover, the prevalence of DPN in the first, second, third and fourth quartiles of CEA level was 12.9%, 19.0%, 29.4% and 40.4%, respectively (p for trend < 0.001); the corresponding adjusted odds ratios and 95% CIs for DPN in CEA quartiles were 1, 1.47 (0.45-4.82), 1.72 (0.54-5.53) and 4.58 (1.39-15.06), respectively. Furthermore, the optimal cut-off value of high-normal serum CEA to discriminate DPN was ≥ 2.66 ng/mL, with a Youden index of 0.28, sensitivity of 66.67% and specificity of 61.00%. CONCLUSIONS: Increased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.

Thyroid Dysfunction as a Predictive Indicator in Camrelizumab of Advanced Esophageal Squamous Cell Carcinoma.

Thyroid dysfunction (TD) induced by programmed death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been widely reported. However, the effects of ICI-induced TD on the survival of patients with esophageal squamous cell carcinoma (ESCC) have not been described. Herein, a retrospective study was conducted, which 82 patients with advanced metastatic or recurrent ESCC treated with camrelizumab were enrolled. Twenty patients (24.4%) experienced TD during camrelizumab treatment with or without chemotherapy. The median onset time of TD was 1.7 months. The incidence of TD was 35.6% in patients who previously received thoracic radiotherapy versus 10.8% in patients who did not (P =0.009). Patients with TD had significantly longer median progression-free survival (5.5 months vs 3.5 months, P =0.035) and overall survival (26.7 months vs 11.5 months, P <0.001). TD is frequently observed in ESCC patients treated with camrelizumab and especially in patients who received radiotherapy previously. ESCC patients with TD during ICIs treatment often have better prognosis.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.

NLRP3-mediated Neuroinflammation Exacerbates Incisional Hyperalgesia and Prolongs Recovery After Surgery in Chronic Stressed Rats.

BACKGROUND: Postoperative pain management has increasingly become a public health problem worldwide. Psychological factors can be considered as independent risk factors for the intensity of postoperative pain and the occurrence of postoperative chronic pain. OBJECTIVES: As stress events could facilitate NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation in the central nervous system, we aimed to explore the role of perioperative NLRP3-mediated neuroinflammation in the exacerbation of incisional hyperalgesia in stressed rats. STUDY DESIGN: Experimental trial in rats. SETTING: Department of Anesthesiology, Shanghai, China. METHODS: All animal experimental procedures were approved by the Animal Care and Use Committee of Shanghai Jiaotong University School of Medicine. This study was conducted in rat models of chronic restraint stress and hind paw incision model. Serum corticosterone level measurement and emotion-related behavioral tests were used to confirm that chronic restraint stress can cause depression-like behavior in rats. Pain behavior after surgery was assessed by withdrawal response to von Frey filament application. Immunofluorescence staining and  the Western blot test were used to evaluate the protein level of NLRP3, IL-1beta, C-fos in the basolateral amygdala (BLA) and GluN2B-containing N-methyl-D-aspartate (NMDA) receptors (GluN2B) expression in the central nucleus of the amygdala (CeA), respectively. Intra-BLA cannulation and microinjection of an NLRP3 specific inhibitor--MCC950 (0.5 µL, 2 µg/µL) were applied to the stressed rats for 4 days perioperatively to explore whether the stress-induced postoperative hyperalgesia and GluN2B expression in CeA can be altered. RESULTS: The results showed that chronic restraint stress exposure led to depressive behavior in rats. Moreover, chronic restraint stress exposure increased NLRP3 and interleukin 1 beta (IL-1beta) expression in the basolateral amygdala (BLA), as well as exacerbated postoperative hyperalgesia and prolonged the recovery time of postoperative pain. Meanwhile, GluN2B expression in the CeA of the stressed group was higher than that of the control incision group. Inhibition of NLRP3 reversed the exacerbation of postoperative hyperalgesia by stress exposure, and down-regulated GluN2B expression in the CeA. LIMITATIONS: The upstream mechanism by which NLRP3 is elevated in stressed rats was not explored. CONCLUSION: These findings suggest that chronic restraint stress may influence postoperative hyperalgesia and NLRP3-mediated neuroinflammation, which may in turn contribute to stress-induced postoperative pain exacerbation.

Radiation Effects in the Crystalline-Amorphous SiOC Polymer-Derived Ceramics: Insights from Experiments and Molecular Dynamics Simulation.

Radiation-tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Nanostructuring is a key strategy to improve the radiation tolerance of materials. SiOC polymer-derived ceramics (PDCs) are unique synthetic nanocomposites consisting of ß-SiC nanocrystals and turbostratic graphite distributed in amorphous SiOC matrix, which are "all-rounder" materials for many advanced structural and functional applications. Radiation effects in the crystalline-amorphous system have been investigated in detail by experiments and molecular dynamics (MD) simulations. The results indicate that the amorphous SiOC structure retains amorphous accompanied by redistribution of the Si-containing tetrahedra. The graphite is shown to amorphize more easily than ß-SiC nanocrystals under the same irradiation condition. The sample richer in oxygen, namely, containing more amorphous SiOC, shows less disordering of graphite, resulting from greater mitigation of radiation damage by the amorphous phase as efficient sinks. This study provides details of the microstructure evolution of SiOC PDCs under ion irradiation, as well as insights for the design and development of advanced ion damage-resistant materials.

Cognitive assessment tools for mild cognitive impairment screening.

Mild cognitive impairment (MCI) is a clinical condition with a high risk of progression to dementia. Due to lack of effective disease-modifying therapies for advanced dementia, diagnosis and disease intervention at an early stage, particularly at MCI stage, has been widely accepted as a critical strategy in disease management that could potentially affect long-term outcome. However, there is currently no consensus on guidelines for routine screening of MCI, resulting in a considerable number of patients with undiagnosed MCI from community. In addition, the use of different screening guidelines leads to difficulties in comparing different studies. A variety of screening tools have been utilized; however, the sensitivity and specificity vary greatly among these tools. By summarizing the sensitivity, specificity and time efficiency for common MCI screening tools, which are key factors to be taken into consideration when making selections and combinations of screening tools, this review suggests the use of a combination of two self-administered highly sensitive tools, p-AD8 + IQCODE (informant questionnaire on cognitive decline in the elderly individuals) in initial screening, as well as a combination of two highly specific widely covered tools, DemTect + MoCA (Montreal cognitive assessment) or memory and executive screening (MES) + MoCA in secondary screening. In addition, this review also proposes a screening flowchart for MCI, aiming to build a sensitive and time efficient way for recruiting subjects for subsequent investigation and disease differentiation.

Exosomal LncRNA-NEAT1 derived from MIF-treated mesenchymal stem cells protected against doxorubicin-induced cardiac senescence through sponging miR-221-3p.

BACKGROUND: The chemotherapy drug doxorubicin (Dox) is widely used for treating a variety of cancers. However, its high cardiotoxicity hampered its clinical use. Exosomes derived from stem cells showed a therapeutic effect against Dox-induced cardiomyopathy (DIC). Previous studies reported that exosomes derived from mesenchymal stem cells (MSCs) pretreated with macrophage migration inhibitory factor (MIF) (exosomeMIF) showed a cardioprotective effect through modulating long noncoding RNAs/microRNAs (lncRNAs/miRs). This study aimed to investigate the role of exosomeMIF in the treatment of DIC. RESULTS: Exosomes were isolated from control MSCs (exosome) and MIF-pretreated MSCs (exosomeMIF). Regulatory lncRNAs activated by MIF pretreatment were explored using genomics approaches. Fluorescence-labeled exosomes were tracked in vitro by fluorescence imaging. In vivo and in vitro, miR-221-3p mimic transfection enforced miR-221-3p overexpression, and senescence-associated ß-galactosidase assay was applied to test cellular senescence. Exosomal delivering LncRNA-NEAT1 induced therapeutic effect in vivo was confirmed by echocardiography. It demonstrated that exosomesMIF recovered the cardiac function and exerted the anti-senescent effect through LncRNA-NEAT1 transfer against Dox. TargetScan and luciferase assay showed that miR-221-3p targeted the Sirt2 3'-untranslated region. Silencing LncRNA-NEAT1 in MSCs, miR-221-3p overexpression or Sirt2 silencing in cardiomyocytes decreased the exosomeMIF-induced anti-senescent effect against Dox. CONCLUSIONS: The results indicated exosomeMIF serving as a promising anti-senescent effector against Dox-induced cardiotoxicity through LncRNA-NEAT1 transfer, thus inhibiting miR-221-3p and leading to Sirt2 activation. The study proposed that exosomeMIF might have the potential to serve as a cardioprotective therapeutic agent during cancer chemotherapy.

Dissecting the Interaction of FGF8 with Receptor FGFRL1.

In mammals, the novel protein fibroblast growth factor receptor-like 1 (FGFRL1) is involved in the development of metanephric kidneys. It appears that this receptor controls a crucial transition of the induced metanephric mesenchyme to epithelial renal vesicles, which further develop into functional nephrons. FGFRL1 knockout mice lack metanephric kidneys and do not express any fibroblast growth factor (FGF) 8 in the metanephric mesenchyme, suggesting that FGFRL1 and FGF8 play a decisive role during kidney formation. FGFRL1 consists of three extracellular immunoglobulin (Ig) domains (Ig1-Ig2-Ig3), a transmembrane domain and a short intracellular domain. We have prepared the extracellular domain (Ig123), the three individual Ig domains (Ig1, Ig2, Ig3) as well as all combinations containing two Ig domains (Ig12, Ig23, Ig13) in recombinant form in human cells. All polypeptides that contain the Ig2 domain (Ig123, Ig12, Ig23, Ig2) were found to interact with FGF8 with very high affinity, whereas all constructs that lack the Ig2 domain (Ig1, Ig3, Ig13) poorly interacted with FGF8 as shown by ELISA and surface plasmon resonance. It is therefore likely that FGFRL1 represents a physiological receptor for FGF8 in the kidney and that the ligand primarily binds to the Ig2 domain of the receptor. With Biacore experiments, we also measured the affinity of FGF8 for the different constructs. All constructs containing the Ig2 domain showed a rapid association and a slow dissociation phase, from which a KD of 2-3 × 10-9 M was calculated. Our data support the hypothesis that binding of FGF8 to FGFRL1 could play an important role in driving the formation of nephrons in the developing kidney.

Field-Induced Wettability Gradients for No-Loss Transport of Oil Droplets on Slippery Surfaces.

Transporting oil droplets is crucial for a wide range of industrial and biomedical applications but remains highly challenging due to the large contact angle hysteresis on most solid surfaces. A liquid-infused slippery surface has a low hysteresis contact angle and is a highly promising platform if sufficient wettability gradient can be created. Current strategies used to create wettability gradient typically rely on the engineering of the chemical composition or geometrical structure. However, these strategies are inefficient on a slippery surface because the infused liquid tends to conceal the gradient in the chemical composition and small-scale geometrical structure. Magnifying the structure, on the other hand, will significantly distort the surface topography, which is unwanted in practice. In this study, we address this challenge by introducing a field-induced wettability gradient on a flat slippery surface. By printing radial electrodes array, we can pattern the electric field, which induces gradient contact angles. Theoretical analysis and experimental results reveal that the droplet transport behavior can be captured by a nondimensional electric Bond number. Our surface enables no-loss transport of various types of droplets, which we expect to find important applications such as heat transfer, anticontamination, microfluidics, and biochemical analysis.

Total in vitro biosynthesis of the nonribosomal macrolactone peptide valinomycin.

Natural products are important because of their significant pharmaceutical properties such as antiviral, antimicrobial, and anticancer activity. Recent breakthroughs in DNA sequencing reveal that a great number of cryptic natural product biosynthetic gene clusters are encoded in microbial genomes, for example, those of Streptomyces species. However, it is still challenging to access compounds from these clusters because many source organisms are uncultivable or the genes are silent during laboratory cultivation. To address this challenge, we develop an efficient cell-free platform for the rapid, in vitro total biosynthesis of the nonribosomal peptide valinomycin as a model. We achieve this goal in two ways. First, we used a cell-free protein synthesis (CFPS) system to express the entire valinomycin biosynthetic gene cluster (>19 kb) in a single-pot reaction, giving rise to approximately 37 µg/L of valinomycin after optimization. Second, we coupled CFPS with cell-free metabolic engineering system by mixing two enzyme-enriched cell lysates to perform a two-stage biosynthesis. This strategy improved valinomycin production ~5000-fold to nearly 30 mg/L. We expect that cell-free biosynthetic systems will provide a new avenue to express, discover, and characterize natural product gene clusters of interest in vitro.

CD5L-induced activation of autophagy is associated with hepatoprotection in ischemic reperfusion injury via the CD36/ATG7 axis.

Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that is difficult to prevent. I/R injury induces metabolic strain on hepatocytes and limits the tolerable ischemia during liver resection, as well as preservation times during transplantation. Additionally, I/R injury induces apoptosis in hepatocytes. CD5-like (CD5L), an inducer of autophagy, is a soluble scavenger cysteine-rich protein that modulates hepatocyte apoptosis. The aim of the present study was to determine if pharmacologic CD5L was protective against hepatic ischemia-reperfusion injury. Hepatocytes were subjected to I/R culture conditions, and apoptosis and caspase family activity were measured after I/R to model hepatic injury. Treatment with recombinant CD5L significantly suppressed apoptosis and caspase activity through modulating cellular autophagy to maintain activation of the cluster of differentiation 36 (CD36)-dependent autophagy-related 7 (ATG7) signaling pathway. The regulation loop between CD5L and the autophagy signaling pathway was identified to be associated with the inhibition of oxidative stress. Treatment with CD5L significantly inhibited cellular oxidative stress, which was confirmed by silencing the CD36 receptor or the autophagy related protein ATG7 using small interfering RNA, which reversed the antiapoptotic and antioxidative effects of CD5L on hepatocytes under I/R conditions. The results of the present study suggested that CD5L-mediated attenuation of hepatic I/R injury occurs through the CD36-dependent ATG7 pathway, accompanied by the inhibition of oxidative stress, which is associated with enhanced autophagy. In conclusion, the present study identifies CD5L as a novel therapeutic agent for hepatic I/R injury.

Modeling of Oil/Water Interfacial Dynamics in Three-Dimensional Bistable Electrowetting Display Pixels.

Electrowetting has drawn significant interest because of the potential applications of displays, lab-on-a-chip microfluidic devices, electro-optical switches, and so forth. However, electrowetting display (EWD) is monostable, which needs extra continuous voltage supply to keep contracting the oil. This paper is concerned with the simulation of two-phase liquid flow in three-dimensional EWD pixels with two electrodes (E1 and E2) demonstrating bistability, where power is only needed to move the oil droplet between two stable states. The effects of E1 geometry, E2 geometry, and E2 pulse characteristics on the dynamics of the oil droplet motion have been analyzed. Also, predictions of the transient states in four stages of the reversible bistable operation process have been carried out by employing the finite element method, in qualitative agreement with our experimental results of the monostable EWD and the existing literature. We seek to shed more light on the fundamental two-phase liquid flow in three-dimensional pixels exhibiting bistability for low power EWD and guide optimizing the electrodes to the perfect patterns with the aid of rigorous modeling.

Plasma parameters and risk factors of patients with post-stroke cognitive impairment.

BACKGROUND: It is high of the incidence of stroke and dementia with the advent of an aging society. Post-stroke cognitive impairment is one of the common complications of stroke, which not only seriously affects the life quality of patients, but also significantly reduces the survival time of stroke patients. Moreover, it also brings in heavy burden to the family and society. The development of vascular dementia could be reduced by early intervention after stroke. Management of vascular risk factors could be an effective way to prevent dementia. This study aimed to investigate the plasma biochemical parameters of post-stroke cognitive impairment (PSCI) and its potential risk factors. METHODS: Four hundred eighty-seven consecutive patients with ischaemic stroke were included and followed up for 3 years. Among these patients, 132 cases were diagnosed as PSCI. The cognitive impairment of patients with PSCI was assessed by the Mini Mental State Examination and Montreal cognitive assessment scale. The plasma biochemical parameters and blood coagulation, as well as computed tomography and magnetic resonance imaging of all the patients after admission, were measured. RESULTS: Multivariate analyses revealed that increased age, carotid plaque, cerebral atrophy, white matter lesions (WML), alcohol use, smoking and history of systolic blood pressure ≥170 mmHg was highly associated with PSCI (P<0.05). Elevated homocysteine, low-density lipoprotein (LDL), and uric acid were also highly associated with PSCI. Logistic regression analysis identified five risk factors correlated with PSCI including alcohol use [odds ratio (OR): 5.138, 95% confidence interval (CI): 1.014-26.04, P=0.048], history of high systolic blood pressure (OR: 12.171, 95% CI: 3.339-44.363, P=0.001), carotid plaque (OR: 1.692, 95% CI: 1.032-2.796, P=0.040), cerebral atrophy (OR: 2.280, 95% CI: 1.294-4.001, P=0.004), and WML (OR: 3.155, 95% CI: 1.868-5.324, P=0.001). Three plasma biochemical parameters were also associated with PSCI including homocysteine (OR: 1.018, 95% CI: 0.944-1.042, P=0.010), and LDL (OR: 0.83, 95% CI: 0.6-1.148, P=0.051), and uric acid (OR: 1.00, 95% CI: 0.998-1.002, P=0.007). The area under the receiver operating curve for the risk factors of PSCI was 0.821 with the sensitivity of 76.3% and specificity of 71.9%. CONCLUSIONS: Elevated homocysteine, LDL, and uric acid were highly related to PSCI, which may help predict PSCI. These plasma biochemical parameters together with vascular risk factors, may improve the sensitivity for early detection of PSCI.

Distally Based Sural Adipofascial Turnover Flap for Coverage of Complicated Wound in the Foot and Ankle Region.

BACKGROUNDS: Distally based perforator propeller flap from the lower leg region is a versatile local reconstructive technique for the foot and ankle defects. However, flap venous congestion remains a tough nut to crack. We hypothesize that raising an adipofascial flap with turnover mode of transposition can improve venous drainage and enhance flap safety. METHODS: Based on the 2 rows of septocutaneous perforators in the posterior distal third of the lower leg, distally based adipofascial flap was raised from medial sural region nourished by 1 perforator bundle from the posterior tibial artery or from the lateral sural region from the peroneal artery. The superficial dissection was performed in subdermal plane and deep in to the subfascial space. The flap was nourished by perforator-plus-adipofascial pedicle and turned over 180 degrees upside down to reach the distal wounds. One week later, a split-skin graft was used to cover the exposed fascial flap. Postoperatively, flap survival, complications, and patient functional recovery were evaluated. RESULTS: Distally based sural turnover adipofascial flaps were used in 12 cases with complicated wounds of the distal third lower leg, foot, and ankle region. All wounds were caused by trauma and experienced fracture implants fixation and 5 with osteomyelitis. The comorbidities include diabetes in 9 cases and smoking in 7. There were 8 medial ural flaps and 4 lateral sural flaps. The adipofiscial flaps measured from 6.0 cm × 5.0 cm to 17.0 cm × 6.0 cm (mean, 61.3 cm). Postoperatively, all flaps survived uneventfully without any complication such as flap ischemia and/or necrosis. Two minor donor site complications were encountered, one was postoperative hematoma, and another was hyperproliferative scar. After a mean of 14.6 months of follow-up, the adipofascial flap plus skin graft showed a durable esthetic coverage, with normal shoe wearing and walking. CONCLUSIONS: Distally based sural adipofascial turnover flap is a simple and reliable wound coverage technique. It avoids venous congestion as usually seen in distally based fasciocutaneous flaps.