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Oral cancer is a common life-threatening malignancy having high mortality and morbidity rates. During the treatment process, individuals unavoidably experience severe side effects. It is essential to develop safer and more effective strategies. Currently, extracellular vesicles (EVs) and biomimetic nanoparticles are nanomedicines with long-term blood circulation and lower off-target toxicity that orchestrate immune responses and accumulate specifically in tumor sites. EVs create a synergetic effect by encapsulating drugs and collaborating with naturally loaded elements in the EVs. Biomimetic nanoparticles retain the characteristic features of the synthetic nanocarriers and inherit the intrinsic cell membrane functionalities. This review outlines the properties, applications, challenges, pros and cons of EVs and biomimetic nanoparticles, providing novel perspectives on oral cancer.

The prognosis of hepatocellular carcinoma (HCC) remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy. In terms of recent studies, microvascular invasion (MVI) is one of the potential predictors of recurrence. Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning.To develop a radiomic analysis model based on pre-operative magnetic resonance imaging (MRI) data to predict MVI in HCC.A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation, among whom 73 were found to have MVI and 40 were not. All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy. We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI, namely, the regions of interest. Quantitative analyses included most discriminant factors (MDFs) developed using linear discriminant analysis algorithm and histogram analysis with MaZda software. Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis. Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold cross-validation was also appliedThe area under the ROC curve (AUC) of the MDF (0.77-0.85) outperformed that of histogram parameters (0.51-0.74). After multivariate analysis, MDF values of the arterial and portal venous phase, and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI (Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.

During recovery from heat stress, plants clear away the heat-stress-induced misfolded proteins through the ubiquitin-proteasome system (UPS). In the UPS, the recognition of substrate proteins by E3 ligase can be regulated by the N-terminal acetyltransferase A (NatA) complex. Here, we determined that Arabidopsis STRESS-RELATED UBIQUITIN-ASSOCIATED-DOMAIN PROTEIN FACTOR 1 (SUF1) interacts with the NatA complex core subunit NAA15 and positively regulates NAA15. The suf1 and naa15 mutants are sensitive to heat stress; the NatA substrate

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant–pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

Background: The function of lipid droplets (LDs) has not been clarified in precancerous lesions, and the relationship between LDs, lipid metabolism, and epithelial-mesenchymal transition (EMT) remains unclear in the carcinogenesis processes in the oral cavity.Methods: Tissue frozen sections were collected for oil red O staining of LDs. Forty-eight oral squamous cell carcinomas (OSCC), 78 oral potentially malignant disorders (OPMDs), and 25 normal paraffin-embedded tissue sections were included to explore the LDs surface protein caveolin-2 and perilipin-3, lipid metabolism-related molecule fatty acid binding protein 5 (FABP5), and EMT biomarker E-cadherin expression by immunohistochemical staining. Results: The accumulation of LDs was observed in OPMDs and OSCCs compared to normal tissues (P < 0.05). In general, an increasing trend of caveolin-2, perilipin-3, and FABP5 expression was detected from the normal to OPMDs to OSCC groups (P < 0.05); however, the increased level of perilipin-3 was not significant in OPMDs compared to the normal controls (P > 0.05). In addition, caveolin-2, perilipin-3, and FABP5 expression were positively correlated with epithelial dysplasia in OPMDs, whereas E-cadherin positivity was negatively correlated with epithelial dysplasia and histopathological grade in OPMDs and OSCC, respectively. A negative correlation of caveolin-2 (P < 0.01, r = - 0.1739), and FABP5 (P < 0.01, r = - 0.1880) with E-cadherin expression was detected. The caveolin-2 (P < 0.0001, r = 0.2641) and perilipin-3 (P < 0.05, r = 0.1408) staining was positively correlated with FABP5. OSCC local recurrence was associated with high expression of caveolin-2 (P < 0.05) and FABP5 (P < 0.05), and lymph node metastasis was associated with high FABP5 expression (P < 0.05) but low E-cadherin expression (P < 0.05). The caveolin-2 high expression group had a worse disease-free survival (DFS) (P < 0.05). Conclusion: In the oral epithelial carcinogenesis process, LDs begin to accumulate early in the precancerous stage. LDs may be the regulator of FABP5-associated lipid metabolism and are closely related to the process of EMT; caveolin-2 could be the main functional protein, indicating that caveolin-2 is a potential biomarker for oral carcinogenesis and prognosis.

Objective This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). Methods This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS–ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. Results A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0–2) (p = 0.01) and excellent mRS (0–1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. Conclusion IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS.

Background Exosomes exert considerable influence in mediating regulatory T (Treg) cells differentiation, which attach great importance to attenuating acute cellular rejection after liver transplantation (LT). And, miRNAs are known to play essential roles in cell-cell communication delivered by exosomes. However, the function of exosomal miRNAs in regulating Treg cells after LT remains unknown. Here, we performed an expression profiling analysis of exosome-miRNAs from human plasma after LT and investigated their immunoregulatory effects on Treg cells. Methods Fifty-eight LT patients and nine donors were included in this report. miRNA profiles in plasma exosomes were analyzed using next-generation sequencing. Flow cytometry, HE and multiplex immunofluorescent staining were used to identify Treg cells in the liver and peripheral blood. A mouse LT model was employed to confirm the infiltration of Treg cells in the liver and circulation. A lentiviral vector system was used to overexpress miR-193b-3p in dendritic cells (DCs), and exosomes isolated from these transfected cells were co-cultured with spleen lymphocytes in vitro. A quantitative Real-time PCR and enzyme-linked immunosorbent assay were used to detect the expression of cytokines. Results Treg cell infiltration was increased in the liver along with Th17 and CD8 + T cell, and it was down-regulated in peripheral blood in the acute rejection group, an effect confirmed in the mouse LT model. High-throughput sequencing revealed that miR-193b-3p was markedly up-regulated in plasma exosomes of non-rejection LT patients. The NLRP3 inflammasome was screened as a target for miR-193b-3p based on target prediction and functional enrichment analyses. Exosomal miR-193b-3p derived from DCs increased Treg cells as demonstrated in vitro. miR-193b-3p overexpression down-regulated NLRP3 as well as the inflammatory cytokines IL-1β and IL-17A while increasing levels of the cytokines IL-10 and TGF-β. Conclusion DC deriving exosomal miR-193b-3p promoted Treg cells by inhibiting NLRP3 expression. These findings not only provide a new perspective on the mechanisms, but also hold great promise for the treatment or prevention of liver allograft rejection.

Background Cryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF. Objective Atrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study. Methods In this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12‐lead electrocardiogram, a 24‐h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits. Results As of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter‐free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter‐free survival. Conclusions Although CBA and RFA are both effective in left atrial electrical and structural reverse‐remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long‐term follow‐up, there was no significant intergroup difference.

Liver transplantation (LT) is an effective strategy for the treatment of end-stage liver disease, but immune rejection remains a significant detriment to the survival and prognosis of these LT patients. While immune rejection is closely related to cytokines, the cytokines investigated within previous studies have been limited and have not included a systematic analysis of proinflammatory cytokines. In the present study, we used a protein chip system and proteomics to detect and analyze serum proinflammatory cytokines and differentially expressed proteins in liver tissue in a mouse model of liver transplantation. In addition, bioinformatics analysis was employed to analyze the proinflammatory cytokines and differential changes in proteins in response to this procedure. With these analyses, we found that serum contents of GC-CSF, CXCL-1, MCP-5, and CXCL-2 were significantly increased after liver transplantation, while IL-5, IL-10, and IL-17 were significantly decreased. Results from Gene Ontology (GO) and KEGG pathway analyses revealed that the cytokine-cytokine receptor, Th1/Th2 cell differentiation, and JAK-STAT signaling pathway were enriched in a network associated with the activation of immune response. Results from our proteomic analysis of liver tissue samples revealed that 470 proteins are increased and 50 decreased, including Anxa1, Anxa2, Acsl4, Sirpa, S100a8, and S100a9. KEGG pathway analysis indicated that the neutrophil extracellular trap formation, NOD-like receptor signaling pathway, and leukocyte transendothelial migration were all associated with liver transplant rejection in these mice. Bioinformatics analysis results demonstrated that CXCL-1/CXCL-2 and S100a8/S100a9 were the genes most closely related to the functions of neutrophils and the mononuclear phagocyte system. These findings provide new insights into some of the critical factors associated with liver transplant rejection and thus offer new targets for the treatment and prevention of this condition.

Most plants in nature establish symbiotic associations with endophytic fungi in soil. Beneficial endophytic fungi induce a systemic response in the aboveground parts of the host plant, thus promoting the growth and fitness of host plants. Meanwhile, temperature elevation from climate change widely affects global plant biodiversity as well as crop quality and yield. Over the past decades, great progresses have been made in the response of plants to high ambient temperature and to symbiosis with endophytic fungi. However, little is known about their synergistic effect on host plants. The endophytic fungus

ROS1-rearranged non-small cell lung cancer (NSCLC) is a subset of NSCLC patients with unique malignant behavior and clinical course. Crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has promising significant activity in NSCLC with ROS1-rearrangement. The next-generation sequencing (NGS) is commonly used to identify the “druggable” genetic alterations in clinical practice. We identified a novel ROS1 fusion variant (FRK-ROS1) in a de novo stage IV NSCLC patient by NGS testing. This novel ROS1-rearrangement is generated by the fusion FRK to ROS1. The patient was remarkably responsive to crizotinib including the brain metastasis. A 29-year-old male never-smoker with chief complaints of back pain with a lumpy and flaky soft tissue mass in the upper right lobe of the lung and diffuse ground-glass shadow in both lungs e IV (cT4N3M1b). A CT-guided biopsy revealed the predominant adenocarcinoma and partial mucinous adenocarcinoma. By using next-generation sequencing (NGS) assay, we found that the tumor had FRK-ROS1 fusion rather than other actionable mutations. In that case, the patient took the first-line crizotinib and experienced a remarkable tumor response to it and tolerance well until written. FRK-ROS1 is a novel ROS1 fusion variant in NSCLC identified by NGS testing and the first-line crizotinib showed excellent performance in all lesions including the brain metastasis.

BACKGROUND Portopulmonary hypertension (PoPH) is not uncommon in patients waiting for liver transplantation (LT). Severe PoPH has a very high perioperative mortality rate and is still considered a contraindication for LT. Many patients with liver disease require but cannot receive LT due to severe PoPH and eventually died. We report a patient with severe PoPH who underwent successful LT and had near normal pulmonary pressure without drug treatment. CASE SUMMARY A 39-year-old woman was hospitalized with the chief complaint of jaundice and exertional dyspnea and fatigue. Caroli disease and liver cirrhosis was diagnosed 6 years previously. Her liver disease met the criteria for LT. However, right heart catheterization showed that her mean pulmonary artery pressure was increased at 50 mmHg, pulmonary vascular resistance was 460 dyn∙s/cm5 and pulmonary artery wedge pressure was 20 mmHg, which may have been the reasons for her chief complaint. The patient was diagnosed with severe PoPH and was not listed for LT immediately. After 5 mo of pharmacotherapy, her severe PoPH was moderate, and she underwent successful LT. Pulmonary artery pressure steadily decreased according to post-operative echocardiographic monitoring and drugs have been discontinued for a month. CONCLUSION The safety of LT can be greatly improved by reducing mean pulmonary artery pressure to a low level, and LT may cure PoPH.

Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

BACKGROUND: There are few detailed consensus and guidelines on perioperative clinical characteristics of liver transplantation (LT) in patients with methylmalonic acidemia (MMA). This retrospective study investigated details of the clinical course and individualized treatment plan of the center with largest experience in China. METHODS: A total of 7 MMA patients undergoing LT in Beijing Friendship Hospital from June 2013 to December 2017 were enrolled in the study, whose clinical data (clinical characteristics, laboratory findings, chronological changes in urine MMA levels, treatment, etc.) during perioperative period were analyzed retrospectively. All the patients received strict postoperative management. RESULTS: All the 7 cases were confirmed to have isolated MMA, among which, 3 cases received living donor liver transplantation (LDLT), 4 cases received deceased donor liver transplantation (DDLT). A wild fluctuate of metabolic condition was observed within the first few days after surgery and two weeks after LT, the mean base excess of blood value (BE-B) restored to normal whereas plasma bicarbonate (HCO(3)(−)) was still below normal value even with intermittent sodium bicarbonate correction. It also showed marked reduction in propionylcarnitine (C3) and C3/C2 level and the mean urine MMA by gas chromatography-mass spectrometry (GC-MS) was reduced by 81.7% (P72× higher than upper limit of normal. The metabolism-correcting medications were administered as before. The renal function of one case with renal insufficiency before LT (serum creatinine rising) maintained stable by adjusting the immunosuppressive regimen during the observation period. All patients survive to date. CONCLUSIONS: LT is an effective treatment to prevent metabolic crisis, but patients with MMA tend to be metabolically fragile even after surgery. During perioperative period, close monitoring should be given for acidosis episodes so as to implement sodium bicarbonate correction. Metabolism-correcting medications are still needed. Special immunosuppressive regimen is an effective way of maintaining renal function for those with kidney dysfunction.

Recent evidences demonstrate that dysregulated expression of microRNA-320d (miR-320d) has been associated with several cancer development and progression. However the effect of miR-320d on gastric cardiac adenocarcinoma (GCA) and the association of miR-320d with its potential gene target FoxM1 remain unclear. Here, we evaluated expression profile of miR-320d and FoxM1 in 60 human GCA tissues and GCA cell lines (OE-19 and SK-GT2). Immunohistochemistry, qualitative PCR and western-blotting were performed in GCA tissues to detect the expression level of miR-320d and FoxM1. CCK-8, transwell, wound-healing assays, and in vivo experiments were conducted using GCA cells that treated with miR-320d mimics or inhibitors to evaluate the biological functions of miR-320d. Luciferase reporter assay was conducted to confirm possible binding sites of FoxM1 for miR-320d. Compared with paired non-cancerous tissues, it showed that miR-320d expression was significantly decreased in GCA specimens (P P

Objective The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI). Materials and methods Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2. Results The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1β in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group. Conclusion EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

An iterative hybrid of finite element boundary integral (FEBI) method and physical optics (PO) is presented for scattering problems of complex structures having junctions with electrically large-scale platform. The treatment of basis functions on the junctions between complex structures and platform is discussed in detail. Moreover, the multilevel fast multipole algorithm and the adaptive cross approximation method are employed to accelerate the solution of FEBI and the computation of interaction between FEBI and PO regions, respectively. Compared with FEBI method, the hybrid method can efficiently reduce the number of unknowns and the computational complexity while preserving acceptable accuracy. In addition, the alternative implementation of FEBI and PO can also maintain good independence of the two methods. Some numerical results are discussed to demonstrate the efficiency and accuracy of the approach.

Aim: To develop nanomedicines for immuno-therapy of oral dysplasia and oral squamous cell carcinoma. Materials & methods: All-trans retinoic acid (ATRA)-poly(lactide-co-glycolide acid) (PLGA)-poly(ethylene glycol) (PEG)-programmed death-ligand 1 (PD-L1) nanomedicines were fabricated by loading ATRA into PLGA-PEG nanocarriers and modification using an anti-PD-L1 antibody. Results: ATRA-PLGA-PEG-PD-L1 nanoparticles showed fast cellular uptake, significantly inhibited proliferation and induced apoptosis in DOK and CAL27 cells. Moreover, in C3H tumor-bearing mice, ATRA-PLGA-PEG-PD-L1 nanoparticles more specifically targeted tumor cells, enhanced anticancer activity and reduced side effects when compared with free ATRA. Furthermore, CD8+ T cells were activated around PD-L1 positive cells in the tumor microenvironment after treatment. Conclusion: ATRA-PLGA-PEG-PD-L1 nanoparticles had low toxicity, high biocompatibility and specifically targeted oral dysplasia and squamous carcinoma cells both in vitro and in vivo.

Background and objectives The aim of this study was to analyze risk factors for failure of subclavian vein catheterization. Methods A retrospective analysis of 1562 patients who underwent subclavian vein puncture performed by the same experienced operator at Peking University Cancer Hospital from January 1, 2016 to January 1, 2019 was conducted. The success or failure of subclavian vein catheterization was registered in all cases. Various patient characteristics, including age, gender, body mass index (BMI), preoperative hemoglobin, preoperative hematocrit, preoperative mean corpuscular hemoglobin concentration (MCHC), preoperative albumin, preoperative serum creatinine, puncture needles from different manufacturers and previous history of subclavian vein catheterization were assessed via univariate and multivariate analyses. Results For the included patients, landmark-guided subclavian vein puncture was successful in 1476 cases and unsuccessful in 86 cases (success rate of 94.5%). Successful subclavian vein catheterization was achieved via right and left subclavian vein puncture in 1392 and 84 cases, respectively. In univariate analyses, age and preoperative hemoglobin were associated with failure of subclavian vein catheterization. In a multivariate analysis, aged more than 60 years was a risk factor while the central venous access with Certofix® was associated with an increased rate of success (p-values of 0.001 and 0.015, respectively). Conclusions This study has demonstrated that patient aged more than 60 years was a risk factor for failure of subclavian vein catheterization while the central venous access with Certofix® was associated with an increased rate of success.

Yi Ru,1–4 Xiao-Jie Chen,5 Wen-Zhi Guo,1–4 She-Gan Gao,5 Yi-Jun Qi,5 Pan Chen,5 Xiao-Shan Feng,5 Shui-Jun Zhang1–4 1Henan Key Laboratory of Digestive Organ Transplantation, 2Open Laboratory of Key Disciplines of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation, 3Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplant Medicine, 4Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 5Henan Key Laboratory of Cancer Epigenetics; Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China Background: Liver cancer is a type of malignant tumor with high morbidity and mortality in People’s Republic of China. Its occurrence and development involve the variation and expression changes of multiple genes, and the pathogenesis and related regulatory networks are complex. Purpose: In the present research, we investigate the involvement of NEAT1_2 and SFPQ in cisplatin resistance in liver cancer. The effects of LncRNA NEAT1 and SFPQ expression on the chemotherapeutic resistance of liver cancer cells were analyzed. Methods: The expression level of NEAT1_2 and SFPQ mRNA in tissue specimens or cell lines were examined by RT-qPCR and western blotting. CCK-8 assay was performed to evaluate cell viability. Cell proliferation was performed using the EdU cell proliferation assay. Results: Our data showed that increase NEAT1_2 and SFPQ expressions in liver cancer specimens were associated with the development of cisplatin resistance; high SFPQ expression level impaired patients’ survival from liver cancer. Gain-and loss-of function assay using NEAT1_2 knock-in and knock-out cells constructed using CRISPER/Cas9 system revealed that NEAT1_2 is essential for liver cancer cell survival and mediates cisplatin resistance in liver cancer cells at least partially through SFPQ. Artificial change in NEAT1_2 expression level didn’t significantly influence SFPQ transcription or translation level. Conclusion: Our data revealed NEAT1_2—SFPQ axis as a novel cisplatin resistance mechanism in liver cancer cells in vitro. Keywords: NEAT1, NEAT1_1, NEAT1_2, SFPQ, liver cancer, cisplatin resistance

Adaptive process of finite-element method always needs to solve a set of linear systems repeatedly. This communication proposes an accurate and efficient domain decomposition method (DDM) based on a multilevel algorithm and a coarse-level correction strategy. Our developed algorithm facilitates the adaptive refinement process utilizing dynamic coarse-level correction, exploits the hierarchical feature of the refined systems through p-type multigrid method in subdomains, then solves the lowest order system through algebraic multigrid method in auxiliary and node-based spaces. The numerical results show that with this effective coarse-level correction, the residual errors introduced by adaptive refined systems can be eliminated quickly by the DDM. Besides, optimal performance in terms of simulation time is achieved, regardless of workload imbalances during the adaptive steps. Several large-scale electromagnetic problems are analyzed for accuracy as well as performance evaluation of the proposed method.

The purpose of this study was to investigate the residue elimination of ceftiofur hydrochloride in milk of postpartum cows after intramammary infusing at dry-off. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to detect ceftiofur hydrochloride residue in milk. Through preprocessing, ceftiofur hydrochloride was derivatized into a more stable compound dedfuroyl ceftiofur acetamide (DCA) for further analysis. The linear range of DCA was 0.1 to 50 μg kg−1. Average recoveries of DCA were 82.52–105.86%. The intra-day and interday coefficients of variation (CV) were 2.95–9.82 and 6.41–7.43%, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) scores were 0.05 and 0.1 μg kg−1, respectively. These parameters showed this method was reliable and valid. Twelve cows were administrated 10 mL ceftiofur hydrochloride by intramammary infusion (corresponding to 500 mg ceftiofur) to each udder after the last milking before the dry-off period. Milk was collected from each udder of cow at 12, 24, 36, 48, 60 and 72 h after calving and was mixed for each time point and each cow, then subjected to UPLC-MS/MS analysis. The results showed, the DCA concentrations in all milk samples were less than LOQ and the maximum residue limit (MRL) 100 μg kg−1, which suggested the withdrawal time of ceftiofur hydrochloride intramammary infusion used for preventing and curing mastitis in dry cows was 0 day. The study provided guidance for the clinical applications of ceftiofur hydrochloride intramammary infusion (dry cow).

// Yi Ru 1, * , Xiao-jie Chen 2, * , Zhi-Wei Zhao 1 , Peng-Fei Zhang 1 , Shuai-Hao Feng 1 , Qiang Gao 1 , She-Gan Gao 1, 2, 3, 4 and Xiao-Shan Feng 1, 3, 4 1 The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology , Luoyang, Henan 471003, China 2 Medical College, Henan University of Science and Technology , Luoyang, Henan 471003, China 3 Henan Key Laboratory of Cancer Epigenetics, Henan University of Science and Technology , Luoyang, Henan 471003, China 4 Cancer Institute, Henan University of Science and Technology , Luoyang, Henan 471003, China * These authors contributed equally to this work and co-first authors Correspondence to: Xiao-Shan Feng, email: fengxiaoshan880923@163.com Keywords: gastric cardia adenocarcinoma, p57 kip2 , cyclinD1, clinical stage, different degrees of differentiation Received: February 21, 2017 Accepted: April 19, 2017 Published: May 19, 2017 ABSTRACT Objective: This study aims to investigate the expression and significance of p57 kip2 and cyclinD1 in gastric cardia adenocarcinoma (GCA). p57 kip2 is a negative regulator in the cell cycle. On the contrary, cyclinD1 is a positive regulator of cell cycle progression. Methods: Thirty-two cases of GCA tissues and adjacent non-cancerous tissues were collected for this study. Immunohistochemistry and fluorescence qualitative PCR was used to determine the level of p57 kip2 and cyclinD1 in GCA and its adjacent non-cancerous tissues. Furthermore, the correlation between the mRNA/protein and GCA clinical pathologic parameters were analyzed, and the ralationship of p57 kip2 and cyclinD1 in GCA were also evaluated. Results: The expression of p57 kip2 significantly lower in GCA ( P = 0.036), and there was a significant correlation in the different degrees of differentiation ( P < 0.05). Furthermore, median survival time was 41 months for patients with high mRNA expression of p57 kip2 . This was longer compared to patients with low mRNA expression of P57 kip2 (37 months, X 2 = 4.788, P = 0.029).The expression of cyclinD1 was significantly higher in GCA( P = 0.002), and was significant correlated to clinical stage(P

Background We studied the clinical profiles and the risk factors on the prognosis of tumor patients with pulmonary embolism (PE) after the thoracic and abdominal surgery. Methods We retrospectively screened patients who underwent the thoracic and abdominal surgery at the Peking University Cancer Hospital from January 1, 2007 to January 1, 2020. Among them, 115 patients who were diagnosed with PE were enrolled in our study. Cox regression was performed for multivariate adjusted factor analyses. Results The 90-day overall mortality rate was 11.3% in our study. Univariate analysis showed that gender, MPV, shock, oxygenation index and the APACHE II score within 24 hours after diagnosis of PE were statistically significant in the prognosis of PE after the thoracic and abdominal surgery. In multiple cox regression analysis, we found that patients with shock and the APACHE II score within 24 hours after diagnosis of PE were independent risk factors on the prognosis of PE after the thoracic and abdominal surgery (P values of 0.020 and 0.014, respectively). Conclusions Shock and the APACHE II score within 24 hours after diagnosis of PE were independent risk factors on the prognosis of PE after the thoracic and abdominal surgery; however, the study power was limited.

This paper presents a thermal design method of large plate-fin heat exchanger (PFHE) for cryogenic air separation unit (ASU) based on multiple dynamic equilibriums (MDE). The enlarging of PFHE brings cascading thermal design difficulties. Renault number of multi-streams in long passages fluctuates in wide range which generates various working conditions. The fin type of each passage and the Re for flowing streams are pre-set firstly. Using single-banking with top priority, the Recursive Prior Plug-In (RPP) method is proposed to complete permutation of hot streams and cold streams. The preferable passage arrangement is selected and determined according to the variance of the cumulative heat load. The initial temperature of each ordered stream in all the passages is then obtained. The temperature difference sequence between the one-sided adjacent streams is built. The large heat transfer area in plane perpendicular to the flowing direction is divided into MDE according to the temperature difference sequence. For each equilibrium, the heat balance equations between hot quantity and cold quantity are built by Fourier’s law of heat conduction and heat convection. The final equilibrium temperature of each ordered stream in all the passages can be obtained by iterative solving the simultaneous differential equations for all MDE. Each long stream is also divided into MDE along flowing direction and modeled by energy conservation principle in enthalpy change to obtain the actual phase. The heat transfer process about Re is divided into MDE according to the dynamic equilibriums between heat transfer and frictional resistance to determine the optimal fins under different working conditions. The heat transfer experiment is completed to verify the proposed method. The MDE is applicable for various stacking patterns of numerous long hot streams and cold streams under variable working conditions. The proposed method is especially useful for thermal design of large energy-efficient PFHE for ASU.

Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection are closely intertwined, with one-quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8(+) T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV-1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8(+) T cells is an appealing strategy to impose improved anti-MTB/HIV-1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross-reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV-1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199-207 peptide and HIV-1 Env120-128 peptide was screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8(+) T cells using a recombinant retroviral vector. The bispecificity of the TCR gene-modified CD8(+) T cells was demonstrated by elevated secretion of interferon-γ, tumour necrosis factor-α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199-207 or Env120-128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV-1 simultaneously by transfecting CD8(+) T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV-1 coinfected individuals.

Cancer patients undergoing surgery are at high risk of venous thromboembolism (VTE). The occurrence of VTE in Chinese cancer patients admitted to intensive care unit (ICU) for postoperative care is poorly characterized. This study was designed to investigate the incidence of VTE in this population and to evaluate the utility of the Caprini score in risk stratification.2127 consecutive adult patients admitted to a 10-bed surgical ICU (SICU) in a tertiary care academic hospital during a 4-year period (January 1, 2013 - December 31, 2016) were enrolled. Demographic and VTE data were collected. Data for the Caprini risk assessment model (RAM) was used to stratify patients on their risk of VTE.Of the 2127 patients admitted to ICU after cancer surgery, 66 (3.1%) developed symptomatic VTE. There were a total of 32 patients with pulmonary embolism (PE), 51 patients with deep vein thrombosis (DVT) and 17 patients with both conditions. Based on the original Caprini RAM, 99.5% of the patients scored in the "highest risk" category (score ≥5), all patients with VTE were in the "highest risk" category. Further substratification in the "highest risk" category showed the risk of developing VTE events was significantly higher among patients with Caprini score greater than 10, as compared with patients with Caprini score of 5 to 6 (OR 5.63;95%CI 1.27-24.94), 7 to 8 (OR 2.36;95%CI 1.23-4.52 ) or 9 to 10 (OR 2.28;95%CI 1.17-4.44). The percentage of patients receiving double prophylaxis was 16.8% (358/2127), 20 of the 66 VTE patients (30.3%) received double prophylaxis before VTE was diagnosed. Patients with higher Caprini score were more likely to receive double thromboprophylaxis than patients with lower Caprini score (23.4% of patients with Caprini score10 vs 10.8% with Caprini score 5-6).Though accompanied with the subutilizing of chemoprophylaxis, the overall incidence of VTE was relatively low in Chinese cancer patients admitted to ICU for postoperative care. In contrast, the Caprini score was high in this population. The original Caprini RAM was limited to stratify this population, but further substratification of "highest risk" category demonstrated the risk of developing VTE events was significantly higher in patients with Caprini score greater than 10. Future research with high quality evidence should be performed targeting on the accurate risk stratification and optimizing VTE prophylaxis for this population.

We report Al0.8Ga0.2As recessed-window single-photon avalanche photodiodes with high internal single-photon detection efficiency and low dark count probability. External quantum efficiency was increased by a factor of 2 at $\lambda = 405$ nm. Annealing in arsine with hydrogen carrier gas reduced the dark count probability by a factor of 100, to $\sim 10^{-6}$ /gate with a $\sim 5$ ns gate, at room temperature. The activation energies of primary carrier traps, which give rise to afterpulsing, are extracted in a temperature range from 150 to 200 K.

One new cyclic tetrapeptide cyclic-(Tyr-Ala-Leu-Ser) (1) along with four natural compounds firstly obtained 3H-imidazole-4-carboxylic acid (2), 2-methyl-3H-imidazole-4-carboxylic acid (3), 3-ethylidene-6-isopropyl-piperazine-2,5-dione (4), and 3-isobutylidene-6-methyl piperazine-2,5-dione (5) have been isolated from the coral derived endophytic bacteria Brevibacterium sp. L-4 collected from the South China Sea. Their structures were elucidated through spectroscopic techniques including NMR (1D and 2D), MS, and EA, and their relative configurations were also assigned by NMR analysis.

With the development of molecular biological technology, the association between genes and diseases has drawn increasing attention of researchers; the endothelial nitric oxide synthase (eNOS) gene has been reported to be a candidate gene for cardiovascular disease (CHD). The present study aimed to investigate the association between a polymorphism of eNOS and the risk of CHD in young people (≤40 years old), in addition to the underlying mechanism. A total of 234 cases of CHD in young individuals were collected as the CHD group and 228 cases of healthy individuals as the control group. Peripheral blood was collected and the genotype of the eNOS G894T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism, the gene frequency was calculated and the distributions of genotype and allele frequency between the two groups were compared. Bioinformatics tools were employed to analyze the differences in the local protein structures of the eNOS G894T polymorphism and the biological mechanism was preliminary discussed. The results demonstrated that there were significant differences in the distribution of genotype frequency and allele frequency of the eNOS G894T gene polymorphism between the CHD group and control group (P

Most of Tianshan highway is located in Xinjiang where is the high and cold mountain area. Drifting snow and other disaster continue to occur, seriously affecting road traffic. Conventional monitoring is difficult to meet the emergency needs due to the influence of climate, topography, etc. The article selected MODIS data to inverse snow depth and temporal-spatial distribution in Dushanzi-Kuqa region of Tianshan Highway in recent years. Analysis revealed that the snowfall mainly was concentrated from the end of October to the beginning of April in the next year. The snow area is the least in summer of July, but the largest in winter, accounting for about 35.7% of the entire study area, the snow depth in most areas at 12 to 15 cm, the maximum snow cover depth is about 23 cm in the Dushanzi region of Wusu County. The results of study has a very important theoretical and practical significance to monitoring and control of diseases.

// Xiao-Yun Zhang 1, * , Minle Li 2, * , Kai Sun 1, * , Xiao-Jie Chen 1 , Jian Meng 2 , Lifang Wu 2 , Ping Zhang 2 , Xuemei Tong 2 , Wei-Wen Jiang 1 1 Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China 2 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China * These authors contributed equally to this work Correspondence to: Wei-Wen Jiang, e-mail: wwjiang33@hotmail.com Xuemei Tong, e-mail: xuemeitong@shsmu.edu.cn Keywords: GRIM-19, methylation, HNSCC, proliferation, metabolism Received: August 04, 2014 Accepted: November 02, 2014 Published: December 23, 2014 ABSTRACT To identify novel tumor suppressor genes that are down-regulated by promoter hypermethylation in head and neck squamous cell carcinoma (HNSCC), genome-wide methylation profiling was performed using a methylated DNA immunoprecipitation (MeDIP) array in HNSCC and normal mucosa tissue samples. Promoter hypermethylation of the candidate gene, gene associated with retinoid-interferon induced mortality-19 (GRIM-19), was confirmed in HNSCC cell lines. Multivariate regression analysis determined that GRIM-19 hypermethylation was an independent significant factor for HNSCC diagnosis (OR:125.562; P < 0.001). HNSCC patients with lower ratio of GRIM-19/ACTB hypermethylation had increased overall and disease free survival. Furthermore, the optimal cutoff provided 90% sensitivity and 77% specificity of GRIM-19 hypermethylation as a diagnostic marker for HNSCC. Ectopic expression of GRIM-19 in HNSCC cells led to increased oxygen consumption, reduced glycolysis and decreased cell proliferation. HNSCC cells ectopically expressing GRIM-19 displayed increased p53 activity as well as decreased Stat3 and HIF-1α activities. Moreover, GRIM-19 knockdown not only resulted in decreased oxygen consumption and increased aerobic glycolysis but also promoted cell proliferation and tumorigenic capacity in HNSCC cells. Our data indicate that decreased GRIM-19 expression due to promoter hypermethylation may be important in head and neck carcinogenesis by promoting cell proliferation and regulating metabolic activity.