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Fibroblast-like synoviocytes (FLS) obtained from the joint synovium of rheumatoid arthritis (RA) patients exhibit hyperplasia and aggressive inflammatory phenotypes. This study was designed to explore the anti-inflammatory mechanism of IL-6R inhibitor, tocilizumab, in FLS-mediated inflammation in RA from the perspective of non-coding RNAs (ncRNAs). To this end, we sorted primary FLS obtained from the synovium of patients with RA and cultured them in vitro. The cells were then treated with tocilizumab and subjected to lncRNA- and miRNA-seq to identify the ncRNAs regulated by tocilizumab treatment using bioinformatic analysis and experimental verification. Tocilizumab treatment enhanced the expression of lncRNA MIR31HG and reduced that of micoRNA-214 (miR-214). In addition, miR-214 activated the AKT signaling pathway by directly targeting MIR31HG and PTEN. In addition, the tocilizumab-MIR31HG-miR-214-PTEN-AKT axis regulated the proliferation, migration, and production of inflammatory molecules and matrix metalloproteinases (MMPs) in RA-FLS. Furthermore, co-culture experiments showed that this axis could inhibit the inflammatory phenotype of macrophages and protect chondrocytes. In summary, our study shows that tocilizumab suppresses RA-FLS inflammation by regulating the MIR31HG-miR-214-PTEN-AKT pathway, and presents new insights on RA pathogenesis and potential targets for RA therapy.

Background Mortality and complications remain high after acute type A aortic dissection (ATAAD) open surgery and are associated with coagulation dysfunction. Platelets play an important role in the process of coagulation. This study explored the relationship between postoperative platelet counts and 3-year mortality after operation in patients with ATAAD undergoing open aortic repair surgery. Methods Patients with ATAAD who underwent Total Arch Replacement and Frozen Elephant Trunk in Fuwai Hospital from 2011 to 2015 were selected for this study. The perioperative data were collected and sorted through the electronic clinical case system. Multivariate Logistic regression was used to analyze the risk factors for death within three years after surgery. Results A total of 495 patients were included in the analysis. After correction for confounding factors, decreased postoperative platelet count remained an independent factor that was associated with lower mortality (OR = 0.918, 95% CI 0.853–0.988, P = 0.023). Conclusions The study indicated that decreased postoperative platelet count may lead to increased 3-year mortality, in patients with ATAAD who underwent open aortic repair surgery.

Objective Oligodendroglioma is a rare primary malignant brain tumor that has highly variable clinical outcomes. The aim of this study was to investigate demographics, outcomes, and prognostic factors of all oligodendroglioma cases from the Surveillance, Epidemiology, and End Results database to build a clinical prognosis model to predict survival time of patients with oligodendroglioma. Methods Cases diagnosed between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Age, sex, race, insurance, year of diagnosis, marital status, tumor location, tumor size, summary stage, surgery method, and use of radiotherapy and chemotherapy were evaluated with respect to overall survival by univariate and multivariate analysis. A nomogram predicting 5- and 10-year survival probability for oligodendroglioma was constructed and validated. Results After data cleaning, 4568 patients with oligodendroglioma were included. At the time of last follow-up, mean survival times among grade II and grade III oligodendrogliomas were 74 and 39 months, respectively. In multivariate analysis, radiotherapy, age, tumor site, summary stage, and surgery demonstrated independent associations with survival in both cohorts. Race and radiotherapy demonstrated independent associations with survival in grade II oligodendroglioma. Sex and chemotherapy demonstrated independent associations with survival in grade III oligodendroglioma. Independent factors in either cohort were selected to build a clinical nomogram. The C-index for the nomogram was 0.738 (95% confidence interval 0.718–0.757). The calibration curves of 5- and 10-year survival rates showed good agreement between the nomogram predictions and actual observations. Conclusions This study was the first to develop a nomogram for predicting overall survival of patients with oligodendroglioma to help clinicians predict patient prognosis accurately and conduct further treatment.

In this paper, a bi-parametric perturbation method is proposed to solve the kinematic motions of the human walking load simulated by an inverted-pendulum model consisting of a mass point, spring limbs, and roller feet. In order to establish the kinematic motions of the first and second single- and double-support phases, the Lagrangian variation method is used. Given a set of model parameters, desired walking speed, and initial states, the perturbation solution is used to study the influences of roller radius, stiffness, impact angle, walking speed, and mass on the ground reaction forces (Fz and Fxy), step length, cadence, and duration time. The analytical results show that the peak values of Fz and Fxy are proportional to stiffness, impact angle, and walking speed, but inversely proportional to the roller radius.

Background Thallium poisoning is rare and difficult to recognize. Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality. Aim To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning. Methods Five patients who consumed a thallium-contaminated meal were hospitalized in succession, and underwent clinical examinations such as blood tests and electromyography tests. Urine and blood tests confirmed the diagnosis of thallotoxicosis, revealing the occurrence of food poisoning. All patients underwent detoxification treatment, including hemoperfusion (HP) and treatment with Prussian blue (PB). A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge. Results Initially, the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia, which may differ from common peripheral neuropathy. Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients, which further confirmed the diagnosis of poisoning. Treatment with chelating agents was ineffective, while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood. With early diagnosis and intervention, four patients had a good prognosis and no permanent sequelae. One patient developed blindness and disability during the 24-mo follow-up period. Conclusion Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning. HP plus PB is essential to improve the prognosis of thallium-poisoned patients.

Purpose: Recent studies have indicated that Pentraxin-3 (PTX3) is related to invasion, migration and metastasis of gastric cancer cells (GCCs). However, the function of PTX3 in stemness and tumor-associated macrophages (TAMs) polarization in GC has not yet been revealed. Here, we investigated the role of PTX3 in TAMs polarization and stemness in gastric cancer (GC), and further explored the effect of PTX3 on milky spot metastasis of gastric cancer. Methods: PTX3 expression in human gastric cancer tissues was examined with immunohistochemistry (IHC). The influence on stemness of gastric cancer cells was examined by sphere formation assay and western blot. qRT-PCR, IHC and flow cytometry were used to evaluate M1/M2 macrophage signatures. The effects of PTX3 on TAM polarization and milky spots were investigated in vitro and in vivo. The possible mechanism of PTX3 on targeted cytokines and pathway were analyzed by qRT-PCR and western blot. Results: We found that PTX3 was low expressed in gastric carcinoma tissues and associated with stemness and polarization of macrophages. The upregulation of PTX3 inhibited the stemness of GCCs. Furthermore, PTX3 suppressed the polarization of M2 macrophages in the milky spots in vivo and in vitro and inhibited the metastasis of GC into milky spots. PTX3 restrained the expression of interleukin-4 (IL-4) and IL-10 via the inhibition of phosphorylation of the c-Jun N-terminal protein kinase 1/2 (JNK1/2) in GCCs. Conclusion: These results revealed a novel mechanism of PTX3 in GC, which may participate in the development and metastasis of GC by affecting stemness and macrophage polarization. PTX3 should be considered as a crucial biomarker and may be potentially used in targeted therapy in GC progression.

miR-17-5p has been proved that play important roles in many kinds of tumors progression. This study aimed at explore the function and mechanism of miR-17-5p in thyroid cancer (TC). RT-qPCR was used to detect miR-17-5p and Early growth response 2 (EGR2) expression in TC tissues and cells. CCK8 and colony formation assay were used to analyze cell proliferation. Cell migration and cell invasion was detected by Wound-healing assay and Transwell assay. Detection of protein expression using Western blot analysis. Dual-Luciferase assay was used to analyze the relationship between miR-17-5p and EGR2. In vivo experiment was performed by establishing Xenograft animal model to observe the function of miR-17-5p. We found that miR-17-5p is significantly increased in thyroid cancer tissues and cells. miR-17-5p inhibition repressed cell proliferation, clonal formation, cell migration, and cell invasion in thyroid carcinoma. Moreover, miR-17-5p inhibition suppressed tumorigenesis in vivo. Dual-Luciferase assay and Western blotting assay further proved that miR-17-5p has a negative regulation to EGR2. EGR2 was decreased in TC tissues and cells. Overexpressed EGR2 inhibited the development of thyroid carcinoma both vivo and in vivo. EGR2 knockdown remarkably decreased the anti-cancer effect of miR-17-5p inhibition. miR-17-5p is a thyroid cancer oncomir by modulation of the EGR2., Graphical abstract

Sugar metabolism is among the most important metabolic processes in soybean; it not only affects growth and development, but also plays a role in drought resistance. As a plant biological regulator, exogenous melatonin is assumed to regulate sugar metabolism. Here, physiological and transcriptomic approaches were used to determine the effects of melatonin on physiological indices and key genes and pathways associated with soybean sugar metabolism under drought stress. In plants subjected to drought stress, melatonin treatment increased dry matter accumulation, reduced malondialdehyde content, and increased the content of metabolized sugars in leaves, thereby enhancing soybean yield. Transcriptome analysis revealed that the genes differentially expressed in plants subjected to melatonin treatment and drought stress were enriched in the KEGG “sucrose and starch metabolism” pathway related to glucose metabolism. Among the differentially expressed genes, we identified 12 significantly altered genes associated with glucose metabolism that played roles in regulating the activities of glucose metabolism-related enzymes. Collectively, our results indicated that melatonin can enhance the output of glucose metabolites and tolerance of soybean subjected to drought stress by regulating the genes associated with glucose metabolism and activation of the related enzymes. Our findings provide a detailed theoretical basis for analyzing the regulatory effects of melatonin on soybean sugar metabolism under conditions of drought stress.

Group 1 CD1-restricted T cells are members of the unconventional T cell family that recognize lipid antigens presented by CD1a, CD1b, and CD1c molecules. Although they developmentally mirror invariant natural killer T cells, they have diverse antigen specificity and functional capacity, with both anti-microbial and autoreactive targets. The role of group 1 CD1-restricted T cells has been best established in Mycobacterium tuberculosis (Mtb) infection in which a wide variety of lipid antigens have been identified and their ability to confer protection against Mtb infection in a CD1 transgenic mouse model has been shown. Group 1 CD1-restricted T cells have also been implicated in other infections, inflammatory conditions, and malignancies. In particular, autoreactive group 1 CD1-restricted T cells have been shown to play a role in several skin inflammatory conditions. The prevalence of group 1 CD1 autoreactive T cells in healthy individuals suggests the presence of regulatory mechanisms to suppress autoreactivity in homeostasis. The more recent use of group 1 CD1 tetramers and mouse models has allowed for better characterization of their phenotype, functional capacity, and underlying mechanisms of antigen-specific and autoreactive activation. These discoveries may pave the way for the development of novel vaccines and immunotherapies that target group 1 CD1-restricted T cells.

Introduction: Pre-transplant irreversible pulmonary hypertension and high pulmonary vascular resistance are generally considered as contraindications for orthotopic heart transplantation due to the high risk of right ventricular dysfunction after transplantation. However, there is no consensus on whether reversible pulmonary hypertension increases the incidence of post-transplant complications and mortality. Case report: A patient with acute heart failure and pulmonary artery occlusion successfully underwent heart transplantation concurrent with pulmonary thromboendarterectomy. Discussion and Conclusion: This case illustrates that heart transplantation concurrent with pulmonary thromboendarterectomy can be performed successfully with meticulous operability assessment, superb surgical technique and careful perioperative management.

Objective To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical activity in ovarian cancer (OvCa). Methods This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naive and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). Results Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2–9) and 6 (5–9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0–6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 [31%]; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 [9%]; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031). Conclusions The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.

This study analyzed and compared variations of the sulcus and otolith outlines of three geographic stocks (Huanghe (Yellow) River estuary (HHE), Jiaozhou Bay (JZB), and Changjiang (Yangtze) River estuary (CJE)) of white croaker Pennahia argentata in northern Chinese coastal waters. The sulcus and otolith outline analyses via elliptical Fourier transform (EFT, i.e. outline analysis) achieved an overall classification rate of 80.4% and 87.2%, respectively. Based on a combination of sulcus and otolith shape indices (SIs) and two derivative ratios, a moderate discriminatory efficiency of 64.7% was obtained. The results indicate that sulcus outline analysis could be used alone to discriminate white croaker stocks, and that both sulcus and otolith outline analyses discriminated the fish stocks at a higher classification rate than the shape indices. The sulcus outline analysis provided complementary information to the whole otolith outline analysis for stock discrimination. Both the sulcus and otolith outline analyses efficiently discriminated between the most geographically separated CJE and HHE stocks, indicating that they could be considered discrete stocks for fishery management.

Background Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed primary non-Hodgkin lymphoma of the spine and can induce spinal compression. Reports of lymphoma arising in bone adjacent to metallic prostheses are increasing. However, to our knowledge, DLBCL arising from a scar after lumbar fusion surgery has not been reported previously. Case Description A 63-year-old man complained of a 2-month history of severe pain in the back and both legs, radiating down to the ankle, similar to sciatica with a past history of L2-S1 decompression and fusion 7 years ago. Imaging revealed an irregular mass in the epidural space and around the internal fixation surgical site, which was initially diagnosed as an epidural infectious abscess. Most of the lesion was completely excised and a detailed immunohistopathologic analysis was performed revealing the diagnosis of a DLBCL. After surgery and chemotherapy, he was discharged without complications. Unfortunately, he died 2 years later because of brain metastasis. Conclusions This case highlights the need to consider malignancy in the differential diagnosis and carefully examine surgical specimens in revision surgery. Further understanding of the role of metal implants in the development of lymphoma is required.

Background Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions first reported in 1956; as of 2019, only 37 cases are available in the MEDLINE/PubMed online databases. BCs usually have no clinical symptoms in the early stage, and their imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination. Case summary A 55-year-old woman presented at our hospital with intermittent epigastric pain. She had a slightly high level of serum carbohydrate antigen 72-4 (CA 72-4). Endoscopic ultrasound found that a cystic mass originated from the submucosa of the posterior gastric wall near the cardia, indicating a diagnosis of cystic hygroma of the stomach. Furthermore, a computed tomography scan demonstrated a quasi-circular cystic mass closely related to the lesser curvature of the gastric fundus with a low density. Because the imaging examinations did not suggest a malignancy and the patient required complete resection, she underwent laparoscopic surgery. As an intraoperative finding, this cystic lesion was located in the posterior wall of the fundus and contained some yellow viscous liquid. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well with normal CA 72-4 levels, and her course was uneventful at 10 mo. Conclusion This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this is the first case of BC to present with elevated CA 72-4 levels.

Objective To study the antipyretic and anti-inflammatory constituents from the active fraction of Reduning (RDN) Injection. Methods In this study, the active fraction of RDN Injection was screened by the LPS-induced mouse endotoxin shock model. The chemical constituents were isolated by chromatography on HP-20 macroporous adsorptive resins, silica gel, ODS columns and reverse phase MPLC and HPLC repeatedly, and their structures were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR, ECD) and chemical methods. Meanwhile, we evaluated the anti-inflammatory activities of the isolates by measuring their inhibitory effects on TNF-α production in LPS stimulated RAW 264.7 macrophages. Results The 95% ethanol eluate of RDN Injection by the macroporous adsorption resin column was proved to be the antipyretic and anti-inflammatory active fraction of this injection. A novel iridoid, named jasminoide A (1), and a new guaiane sesquiterpenoid, named (1R,7R,8S,10R)-7,8,11-trihydroxy-4-guaien-3-one (2), were isolated from Reduning injection, and compound 2 can inhibit TNF-α production with IC50 values of 72.24 µmol/L. Conclusion In this study, two new terpenoids were isolated from Reduning Injection, and compound 2 showed inhibitory activity against LPS-activated TNF-α production in RAW 264.7 cells in vitro.

Inflammatory demyelination in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Besides MS disease-modifying therapy, targeting myelin sheath protection/regeneration is currently a hot spot in the treatment of MS. Here, we attempt to explore the therapeutic potential of Bilobalide (BB) for the myelin protection/regeneration in EAE model. The results showed that BB treatment effectively prevented worsening and demyelination of EAE, accompanied by the inhibition of neuroinflammation that should be closely related to T cell tolerance and M2 macrophages/microglia polarization. BB treatment substantially inhibited the infiltration of T cells and macrophages, thereby alleviating the enlargement of neuroinflammation and the apoptosis of oligodendrocytes in CNS. The accurate mechanism of BB action and the feasibility of clinical application in the prevention and treatment of demyelination remain to be further explored.

Aims Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic post-ganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Methods and results Rat CHF was induced by surgical ligation of the left coronary artery. Lentiviral Cav2.2-α shRNA or scrambled shRNA was transfected in vivo into stellate ganglia (SG) in CHF rats. Final experiments were performed at 14 weeks after coronary artery ligation. Real-time polymerase chain reaction and western blot data showed that in vivo transfection of Cav2.2-α shRNA reduced the expression of Cav2.2-α mRNA and protein in the SG in CHF rats. Cav2.2-α shRNA also reduced Cav2.2 currents and cell excitability of CSP neurons and attenuated cardiac sympathetic nerve activities (CSNA) in CHF rats. The power spectral analysis of heart rate variability (HRV) further revealed that transfection of Cav2.2-α shRNA in the SG normalized CHF-caused cardiac sympathetic overactivation in conscious rats. Twenty-four-hour continuous telemetry electrocardiogram recording revealed that this Cav2.2-α shRNA not only decreased incidence and duration of ventricular tachycardia/ventricular fibrillation but also improved CHF-induced heterogeneity of ventricular electrical activity in conscious CHF rats. Cav2.2-α shRNA also decreased susceptibility to ventricular arrhythmias in anaesthetized CHF rats. However, Cav2.2-α shRNA failed to improve CHF-induced cardiac contractile dysfunction. Scrambled shRNA did not affect Cav2.2 currents and cell excitability of CSP neurons, CSNA, HRV, and ventricular arrhythmogenesis in CHF rats. Conclusions Overactivation of Cav2.2 channels in CSP neurons contributes to cardiac sympathetic hyperactivation and ventricular arrhythmogenesis in CHF. This suggests that discovering purely selective and potent small-molecule Cav2.2 channel blockers could be a potential therapeutic strategy to decrease fatal ventricular arrhythmias in CHF.

The stiffness and the topography of the substrate at the cell–substrate interface are two key properties influencing cell behavior. In this paper, atomic force acoustic microscopy (AFAM) is used to investigate the influence of substrate stiffness and substrate topography on the responses of L929 fibroblasts. This combined nondestructive technique is able to characterize materials at high lateral resolution. To produce substrates of tunable stiffness and topography, we imprint nanostripe patterns on undeveloped and developed SU-8 photoresist films using electron-beam lithography (EBL). Elastic deformations of the substrate surfaces and the cells are revealed by AFAM. Our results show that AFAM is capable of imaging surface elastic deformations. By immunofluorescence experiments, we find that the L929 cells significantly elongate on the patterned stiffness substrate, whereas the elasticity of the pattern has only little effect on the spreading of the L929 cells. The influence of the topography pattern on the cell alignment and morphology is even more pronounced leading to an arrangement of the cells along the nanostripe pattern. Our method is useful for the quantitative characterization of cell–substrate interactions and provides guidance for the tissue regeneration therapy in biomedicine.

Spodoptera frugiperda is a serious threat to global food production. Our previous study demonstrated that Camptothecin (CPT), a bioactive secondary metabolite from Camptotheca acuminata (Decne: Nyssaceae), exhibits adverse impact on the larval midgut of S. frugiperda and inhibits insect growth. However, effects of CPT on fat bodies of S. frugiperda larvae have not been examined yet. In the present study, we found that histological structures of fat bodies of S. frugiperda larvae were damaged in insects treated with CPT. Comparative transcriptomic analyses among different fat body samples from controls and insects treated with 1.0 and 5.0 μg/g CPT were performed. A total of 4212 and 5044 differentially expressed genes (DEGs) were identified in the samples treated with 1.0 and 5.0 μg/g CPT, respectively. Our data indicated that the pathways of detoxification, immune response, fatty acids, chitin, and hormone biosynthesis in fat bodies were affected by CPT treatments based on DEGs. These results provided a comprehensive view of the damage and gene expression changes in fat bodies of S. frugiperda after CPT exposure, which shall be useful to reveal the mechanism of CPT toxicity against S. frugiperda in future.

ObjectiveHeart rate (HR) is a risk factor of mortality in many cardiovascular diseases but no clinical studies have focused on the association between HR and prognosis in patients with acute type A aortic dissection (ATAAD). This study aimed to evaluate the association between HR and long-term mortality and establish the criteria of HR in patients with ATAAD who underwent total aortic arch replacement combined with the frozen elephant trunk (TAR+FET).Design, setting and participantsRetrospective cohort study that studied all consecutive patients with ATAAD who underwent TAR+FET in the Fuwai Hospital between 2009 and 2015.Main outcomes and measures30-day postoperative, and estimated long-term mortality.ResultsOverall, 707 patients with ATAAD who underwent TAR+FET were followed up for a median duration of 29 months (range, 5–77 months). In multivariate logistic analysis, HR (p80 bpm was associated with an almost threefold higher long-term mortality. HRs ≤60, 60–70, 70–80, 80–90, 90–100, 100–110 and >110 bpm were associated with 3.9%, 4.0%, 3.8%, 7.2%, 9.5%, 10.1% and 14.4% yearly risks of death, respectively.ConclusionsHR is a powerful predictor of long-term mortality in patients with ATAAD undergoing TAR+FET. HR >80 bpm is independently associated with elevated long-term mortality for patients with ATAAD.

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.

Oesophageal liposarcomas are particularly rare, accounting for 1.2–1.5% of all gastrointestinal liposarcomas. Surgical resection is the usual treatment. Endoscopic resection is minimally invasive but still controversial. This current case report describes a rare case of a large oesophageal liposarcoma in a 52-year-old male that presented with 10-year history of dysphagia for dry and solid food that was exacerbated by a recent common cold. Thoracoscopic and laparoscopic oesophagectomy was performed. He did not have any dysphagia or dyspnoea 1 week postoperatively. The excised specimen consisted of a polypoid mass measuring 21.0 cm × 5.1 cm. Histological examination confirmed that it was an oesophageal liposarcoma. At 1-year postoperatively, there was no sign of recurrence. Thoracoscopy and laparoscopy can be used to treat large oesophageal masses. Long-term follow-up is required as oesophageal liposarcomas tend to recur.

Background. Circulating tumor cells (CTCs) have been regarded as an independent prognostic marker for metastatic castration-resistant prostate cancer (mCRPC). Its prognostic value, however, in nonmetastatic prostate cancer (NMPC) is still unclear. Purpose. To elucidate whether CTCs can predict the biochemical recurrence (BCR) in NMPC patients following radical prostatectomy (RP) or radiotherapy (RT). Methods. PubMed, Cochrane Database, and Embase and the references in relevant studies were systematically searched. Studies that investigated the correlation of CTCs and BCR in NMPC patients after RP or RT were identified and reviewed. Overall odds ratio (OR) of BCR in such patients with/without CTCs was pooled. We also calculated and pooled overall prevalence of BCR in such CTC-positive patients. Results. In total, 12 studies comprising 1917 participants were eligible for the meta-analysis and showed that the presence of secondary circulating tumor cells (SCTCs) is associated with a higher BCR rate of 59% (95% CI: 22%-88%) in patients with NMPC after RP or RT ( OR = 6.12 ; 95% CI: 2.22-16.85; P < 0.001 ). However, regardless of the presence of primary circulating tumor cells (PCTCs), it has not been shown to be associated with higher BCR. Conclusions. Our research demonstrated that SCTC-positive patients are associated with higher BCR compared to SCTC-negative patients in NMPC. Therefore, it is recommended that NMPC patients undergo CTC surveillance intensively after RP or RT.

Myocardial fibrosis detected by cardiac magnetic resonance (CMR) has been reported in patients with desmin‐related myopathy, although its characteristics remain unclear. Here, we describe a case of desmin‐related restrictive cardiomyopathy wherein CMR imaging revealed myocardial oedema, ischaemia, and fibrosis in the left ventricle; the different types and processes of myocardial injury were detected by CMR. Middle wall left ventricular enhancement may be a feature of late gadolinium enhancement, and the lateral wall is often involved in cases of myocardial injury. CMR is useful for the early detection of cardiac involvement and the prediction of prognosis in patients diagnosed with desmin‐related myopathy.

Background Spodoptera frugiperda is a serious pest that causes devastating losses to many major crops, including corn, rice, sugarcane, and peanut. Camptothecin (CPT) is a bioactive secondary metabolite of the woody plant Camptotheca acuminata, which has shown high toxicity to various pests. However, the effect of CPT against S. frugiperda remains unknown. Results In this study, bioassays have been conducted on the growth inhibition of CPT on S. frugiperda larvae. Histological and cytological changes were examined in the midgut of larvae fed on an artificial diet supplemented with 1.0 and 5.0 µg/g CPT. The potential molecular mechanism was explored by comparative transcriptomic analyses among midgut samples obtained from larvae under different treatments. A total of 915 and 3560 differentially expressed genes (DEGs) were identified from samples treated with 1.0 and 5.0 µg/g CPT, respectively. Among the identified genes were those encoding detoxification-related proteins and components of peritrophic membrane such as mucins and cuticle proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that part of DEGs were involved in DNA replication, digestion, immunity, endocrine system, and metabolism. Conclusions Our results provide useful information on the molecular basis for the impact of CPT on S. frugiperda and for future studies on potential practical application.

Pulsatillae radix, a traditional Chinese medicine (TCM), is often used in combination with florfenicol for treatment of intestinal infection in Chinese veterinary clinics. Anemoside B4 (AB4) is the major effective saponin in Pulsatillae radix. This study aimed to investigate whether the pharmacokinetics of florfenicol in broilers was affected by the combination of AB4. In this study, broilers were given AB4 (50 mg/kg BW), or 0.9% sodium chloride solution by oral administration for 7 days. They were then fed florfenicol orally (30 mg/kg BW) on the eighth day. The results showed that the AUC(0-∞), MRT(0-∞), t1/2z and Cmax of florfenicol were significantly decreased, and the Vz/F and CLz/F were significantly increased by AB4; the mRNA expression levels of CXR, CYP3A37 and MDR1 (except CXR and CYP3A37 in the liver) were up-regulated by AB4. In conclusion, AB4 altered the pharmacokinetics of florfenicol, resulting in lower plasma concentrations of florfenicol, this was probably related to the mRNA expression of CXR, CYP3A37 and MDR1 in the jejunum and liver (except CXR and CYP3A37) increased by AB4. The implications of these findings on the effect of traditional Chinese medicine containing AB4 on the effectiveness of florfenicol in veterinary practice deserve study.

Background There is a lack of information on the presence of volatile organic compounds including p-cymene in foods for dietary exposure assessment. p-Cymene is a monoterpene found in many plant species, which has been used as a flavouring agent in foods and also exhibits antioxidant and antimicrobial properties. While the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has no safety concerns at current levels of intake when used as a flavouring, the current study examines p-cymene levels in foods in general, not just from possible uses as a flavouring, as there could still be a potential health concern if there were high levels of exposure. Results 159 food composite samples from the 2014 Canadian Total Diet Study were analysed for p-cymene using a gas chromatographic-mass spectrometric method after headspace solid-phase microextraction. Concentrations of p-cymene in the composite samples of most food types were generally low, with a maximum level of 73.5 μg g-1 , detected in the composite sample of herbs and spices. Dietary exposures to p-cymene were estimated for different age groups of Canadian populations. Conclusions Although p-cymene was detected in various foods, estimated dietary exposures to p-cymene for different age groups are well below the human intake threshold of toxicological concern established by JECFA of 1800 μg per person per day for structural class I flavours, which includes p-cymene. © 2019 Society of Chemical Industry.

Bufaviruses are small, nonenveloped, single-stranded DNA viruses belonging to the subfamily Parvovirinae. Human bufaviruses were first identified in 2012 in fecal samples from children with diarrhea. A new parvovirus of canines that was first detected in various samples from dogs with enteric and respiratory symptoms in Italy between 2014 and 2018 is closely related to the newly described human bufavirus. To explore the prevalence and genetic diversity of CBuV in Chinese dogs, 540 canine parvovirus (CPV)-positive serum and diarrhea samples were collected in Guangxi Province between 2016 and 2018. Among the samples, 6.25% (5/80) of rectal swabs and 2.5% (5/200) of CPV PCR-positive samples were positive for CBuV. However, the virus was not detected in CPV PCR-negative samples or nasal swabs. Two CBuV isolates were identified from CPV-positive fecal and serum samples by complete sequence analysis, with 99.8%–99.9% NS1 and VP2 protein identity to each another. Sequence analysis indicated that the CBuV GXNN01-2018 isolate VP2 protein shares 99.6% identity with the Italian CBuV ITA/2015/297 isolate and 62.3%–65.5% identity with human bufavirus. Phylogenetic analysis showed that CBuV was significantly distinct from other known bufaviruses and was most closely related to CBuV ITA/2015/297. This is the first report of the existence of CBuV in China, and our findings will strengthen the understanding of the epidemiology of bufaviruses in different animals.

Multiple sclerosis is a T cell-mediated inflammatory, demyelinating disease of the central nervous system, accompanied by neuronal degeneration. Based on the anti-inflammatory effects of Ginkgolide K (GK), a platelet activating factor antagonist, we explored the possible application of GK in the treatment of MS. The results showed that GK effectively ameliorated the severity of experimental autoimmune encephalomyelitis. The intervention of GK inhibited the infiltration of inflammatory cells and demyelination in the spinal cord. At the same time, the expression of the inflammation-related molecules TLR4, NF-κB, and COX2 in the spinal cord was significantly lower in the GK-treated mice, indicating that GK intervention can inhibit the inflammatory microenvironment of the spinal cord in EAE mice. In mouse spleen lymphocytes, GK increased the proportion of regulatory T cells (Treg) and reduced the proportion of T helper 17 cells (Th17), modifying the imbalance between Th17/Treg cells. Additionally, GK shifted macrophage/microglia polarization from M1 to M2 cell type. Importantly, GK inhibited the expression of chemotactic molecules CCL-2, CCL-3 and CCL-5, thereby limiting the migration of inflammatory cells to the spinal cord. Our results provide the possibility that GK may be a promising naturally small molecule compound for the future treatment of MS.

Otolith morphology is widely used for fish stock identification. The sulcus, a structure on the medial side of the otolith, is an important feature in morphological analysis. This study was conducted to evaluate the feasibility of using sulcus morphology for stock identification and to compare its performance with commonly used otolith morphology analysis. Otoliths were collected and analyzed from three geographical groups (the Huanghe (Yellow) River estuary, HHE; the Jiaozhou Bay, JZB; and the Changjiang (Yangtze) River estuary, CJE) of yellow drum Nibea albiflora. The results show that the analysis of sulcus morphology based on shape indices (SIs), elliptic Fourier coefficients (EFc), and a combination of the two parameters identified stocks at overall classification rates of 51.0%, 72.5%, and 73.2%, respectively. These classification rates are similar to those obtained using otolith morphology analysis (57.0%, 73.8%, and 76.5% by SIs, EFc, and their combination, respectively). The findings suggest that sulcus morphology is comparable to the commonly used otolith morphology for identifying stocks of sciaenids, such as the yellow drum. For both otolith and sulcus morphology, EFc could identify the stocks more efficiently than SIs, while the combination of SIs and EFc was even better.

The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloids (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds.

Background: Previously, we observed a strong relationship between circulating serum inflammation proteins in relation to lung cancer diagnosis and risk, both in case–control and prospective cohorts. Low-dose computed tomography (LDCT) screening has a high prevalence of false-positive nodules, thus companion noninvasive biomarkers that can distinguish between benign and malignant nodules could have clinical utility and positive impact on patient outcomes. Methods: We conducted a nested case–control study within the National Lung Screening Trial. Concentrations of 30 inflammation proteins were measured on plasma samples of 262 cases and 528 controls using a highly sensitive and analytically validated electrochemiluminescence V-PLEX immunoassay. Results: Comparing the fourth quartile with the first quartile, we found increased IFNγ and IL12/IL23p40 associated with increased odds of a lung cancer diagnosis [OR 1.89, 95% confidence intervals (CI), 1.16–3.09; OR 2.49, 95% CI, 1.46–4.23, respectively]. Confirming our previous observations, we also detected a relationship between increased IL6, IL8, and C-reactive protein (CRP) with lung cancer diagnosis. These relationships were significant after adjustment for age, gender, race, smoking, body mass index (BMI), family history of lung cancer, and previous diagnoses of inflammatory conditions. However, none of these proteins could distinguish between a benign and malignant lung nodule (IL6: OR 1.25, 95% CI, 0.59–2.64; IL8: OR 1.40, 95% CI, 0.70–2.81; CRP: OR 0.98, 95% CI, 0.45–2.12). Conclusions: We have discovered new associations for IFNγ and IL12/IL23p40 with lung cancer but have no evidence that these proteins can distinguish between benign and malignant lung nodules. Impact: Circulating inflammation proteins are unlikely to have utility as companion LDCT biomarkers.