Angiolipoma in the region of the hypopharynx-esophageal introitus is a rare occurrence. Surgical treatment was performed in the few cases reported in the literature. Endoscopic submucosal dissection ...(ESD) is a minimally invasive treatment for hypopharyngeal and esophageal lesions. Our objective was to evaluate the feasibility, safety, and efficacy of ESD for treatment of angiolipoma at the hypopharynx-esophageal introitus. The patients with submucosal tumors at the hypopharynx-esophageal introitus were diagnosed as angiolipoma by preoperative evaluation with endoscopy, endoscopic ultrasonography, and computed tomography (CT). The patients who were diagnosed with angiolipoma agreed to undergo endoscopic submucosal dissection. Under general anesthesia and endotracheal intubation, ESD was used to remove the lesions. Preoperative, intraoperative, and postoperative data were collected and analyzed to evaluate the feasibility, safety, and effectiveness of endoscopic submucosal dissection. From January 2013 to December 2018, 6 cases of angiolipoma were treated with ESD with a success rate of 100%. The average operation time was 107.0±69.4 minutes. Intraoperative blood loss is the main risk. Endoscopic thermocoagulation successfully stopped bleeding in all cases. Pharyngeal pain and painful swallowing were the main clinical signs. There was no stricture at the hypopharynx-esophageal introitus after the operation. ESD treatment of angiolipoma at hypopharynx-esophageal introitus is feasible, safe, and effective.
Gallbladder cancer (GBC) is a leading cause of cancer-related deaths worldwide, and its prognosis remains poor, with a 5-year survival rate of ~5%. Given the crucial role of microRNAs (miRNAs) in ...cancer metastasis, we aimed to analyze the expression and function of the metastasis-associated miRNA miR-29c-5p in GBC.We validated that expression of miR-29c-5p was significantly downregulated in GBC and was closely associated with lymph node metastasis, overall survival and disease-free survival in 40 GBC patients who were followed clinically. Ectopic overexpression of miR-29c-5p dramatically repressed proliferation, metastasis, and colony formation and induced apoptosis in vitro, and it suppressed tumorigenicity in vivo through the MAPK pathway. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) was identified as a critical effector target of miR-29c-5p. Enforced expression of miR-29c-5p significantly inhibited the expression of CPEB4, and restoration of CPEB4 expression reversed the inhibitory effects of miR-29c-5p on GBC cell proliferation and metastasis. Transforming growth factor-β (TGF-β) upregulated CPEB4 by downregulating miR-29c-5p, leading to MAPK pathway activation. In conclusion, the TGF-β/miR-29c-5p/CPEB4 axis has a pivotal role in the pathogenesis and poor prognosis of GBC, suggesting that miR-29c-5p is a tumor-suppressive miRNA that may serve as potential prognostic biomarker or therapeutic target for GBC.
Objectives
The purpose of this study was to determine the diagnostic and prognostic values of serum KL‐6 levels in Chinese patients with interstitial lung disease (ILDs).
Methods
A total of 1084 ...subjects including 373 cases of ILDs, 584 cases of non‐ILD pulmonary diseases, and 127 healthy individuals were recruited from three clinical centers in China between January 2011 and December 2013. A total of 106 patients undergoing treatments for ILDs in Shanghai Pulmonary Hospital between January 2011 and December 2013 were enrolled. Baseline and posttreatment serum KL‐6 levels were determined.
Results
Serum KL‐6 levels in patients with ILDs were significantly higher than those in patients with non‐ILD pulmonary diseases or in healthy individuals (1492.09 ± 2230.08 U/mL vs 258.67 ± 268.73 U/mL or 178.73 ± 71.17 U/mL, all P < 0.05). At the cut‐off value of 500 U/mL, the sensitivity and specificity of serum KL‐6 as a diagnostic marker for ILDs was 77.75% and 94.51%, respectively. The Kappa value was 0.743 (P < 0.001). The area below the receiver operating characteristic curve was 0.922 with a 95% Confidence interval of 0.904–0.941 (P < 0.001). The posttreatment serum KL‐6 levels significantly reduced in patients with improved ILDs, whereas markedly increased in patients with exacerbated ILDs (All P < 0.05).
Conclusions
Serum KL‐6 levels might be a promising diagnostic biomarker for ILDs in Chinese patients. The prognostic value of serum KL‐6 levels for ILDs remains to be verified by large‐scaled studies.
The Be X-ray pulsar SMC X-3 underwent an extra long and ultraluminous giant outburst from 2016 August to 2017 March. The peak X-ray luminosity is up to
∼
10
39
erg/s
, suggesting a mildly ...super-Eddington accretion onto the strongly magnetized neutron star. It therefore bridges the gap between the Galactic Be/X-ray binaries (
L
X
peak
≤
10
38
erg/s
) and the ultraluminous X-ray pulsars (
L
X
peak
≥
10
40
erg/s
) found in nearby galaxies. A number of observations were carried out to observe the outburst. In this paper, we perform a comprehensive phase-resolved analysis on the high quality data obtained with the
Nustar
and
XMM-Newton
, which were observed at a high and intermediate luminosity levels. In order to get a better understanding on the evolution of the whole extreme burst, we take the
Swift
results at the low luminosity state into account as well. At the early stage of outburst, the source shows a double-peak pulse profile, the second main peak approaches the first one and merges into the single peak at the low luminosity. The second main peak vanishes beyond 20 keV, and its radiation becomes much softer than that of the first main peak. The line widths of fluorescent iron line vary dramatically with phases, indicating a complicated geometry of accretion flows. In contrast to the case at low luminosity, the pulse fraction increases with the photon energy. The significant small pulse fraction detected below 1 keV can be interpreted as the existence of an additional thermal component located at far away from the central neutron star.
Because of rapid change in lifestyle risk factors, cardiovascular disease has become the leading cause of death in China. We sought to estimate the national levels of serum lipids and lipoproteins ...among the Chinese adult population.
We conducted a cross-sectional study in a nationally representative sample of 46 239 adults aged ≥20 years. Fasting serum total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were measured by standard methods. The age-standardized estimates of total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were 4.72 (95% confidence interval, 4.70-4.73), 1.30 (1.29-1.30), 2.68 (2.67-2.70), and 1.57 (1.55-1.58) mmol/L, respectively, in the Chinese adult population. In addition, 22.5% (21.8-23.3%) or 220.4 million (212.1-228.8) Chinese adults had borderline high total cholesterol (5.18-6.21 mmol/L), and 9.0% (8.5-9.5%) or 88.1 million (83.4-92.8) had high total cholesterol (≥6.22 mmol/L). The population estimates for borderline high (3.37-4.13 mmol/L), high (4.14-4.91 mmol/L), and very high (≥4.92 mmol/L) low-density lipoprotein cholesterol were 13.9% (13.3-14.5%) or 133.5 million (127.0-140.1), 3.5% (3.3-3.8%) or 33.8 million (31.2-36.5), and 3.0% (2.8-3.3%) or 29.0 million (26.3-31.8) persons, respectively. In addition, 22.3% (21.6-23.1%) or 214.9 million (207.0-222.8) persons had low high-density lipoprotein cholesterol (<1.04 mmol/L). The awareness, treatment, and control of borderline high or high total cholesterol were 11.0%, 5.1%, and 2.8%, respectively, in the Chinese adult population.
Serum total and low-density lipoprotein cholesterol levels were high and increasing in the Chinese population. Without effective intervention, atherosclerotic cardiovascular diseases may soar in the near future in China.
Posttranslational modifications of nuclear proteins, including transcription factors, nuclear receptors, and their coregulators, have attracted much attention in cancer research. Although ...phosphorylation of oligodendrocyte transcription factor 2 (Olig2) may contribute to the notorious resistance of gliomas to radiation and genotoxic drugs, the precise mechanisms remain elusive. We show here that in addition to phosphorylation, Olig2 is also conjugated by small ubiquitin-like modifier-1 (SUMO1) at three lysine residues K27, K76, and K112. SUMOylation is required for Olig2 to suppress p53-mediated cell cycle arrest and apoptosis induced by genotoxic damage, and to enhance resistance to temozolomide (TMZ) in glioma. Both SUMOylation and triple serine motif (TSM) phosphorylation of Olig2 are required for the antiapoptotic function. Olig2 SUMOylation enhances its genetic targeting ability, which in turn occludes p53 recruitment to Cdkn1a promoter for DNA-damage responses. Our work uncovers a SUMOylation-dependent regulatory mechanism of Olig2 in regulating cancer survival.
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This study suggested that regorafenib suppressed tumor invasion, angiogenesis, anti-apoptosis and proliferation were associated with downregulating of EGFR/PKCδ/AKT/ERK/NF-κB pathway. ...In addition, death receptor dependent (extrinsic apoptosis) and mitochondria dependent (intrinsic apoptosis) apoptosis pathways were both activated by regorafenib treatment.
•Regorafenib suppresses EGF-induced EGFR and NF-κB activity in CRC.•Activation of EGFR and EGFR downstream cascades are effectively diminished by regorafenib.•Regorafenib markedly inhibits expression of NF-κB-mediated proteins.•Regorafenib markedly inhibits invasion potential of CRC and invasion related proteins expression.•Regorafenib suppresses tumor growth and triggeres extrinsic/intrinsic pathways in CT26 and HT29 in vitro and in vivo.
Active epidermal growth factor receptors (EGFR) signaling mediates the progression of colorectal cancer (CRC) through activation of downstream kinases and transcription factors. The increased expression of EGFR was associated with worse prognosis in patients with metastatic CRC (mCRC). Regorafenib, the oral kinase inhibitor approved for the treatment of mCRC, has been shown to reduce activation of downstream kinases of EGFR signal pathway in hepatocellular carcinoma and osteosarcoma. However, whether EGFR inactivation was participates in regorafenib-inhibited progression of CRC still remaining ambiguous. The major purpose of present study was to verify effect of regorafenib on EGFR signaling-mediated progression of CRC. Here, we investigated the effect of regorafenib or erlotinib (EGFR inhibitor) on tumor cell growth, invasion ability, apoptotic, and EGFR signal transduction in CRC in vitro and in vivo. Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Both regorafenib and erlotinib significantly reduced cell invasion ability, activation of protein kinase C-δ (PKCδ), protein kinase B (AKT), extracellular signal-regulated kinases (ERK), and NF-κB. Regorafenib can trigger the inhibition of tumor cell growth and the induction of apoptosis through extrinsic/intrinsic apoptosis pathways. In addition, the expression of NF-κB-mediated proteins involved in tumor progression was also suppressed by regorafenib treatment. Taken together, regorafenib acts as a inhibitor of EGFR signaling that attenuated the activation of EGFR and EGFR related downstream signaling cascades in CRC. Our results suggested that the suppression of EGFR signaling was associated with regorafenib-inhibited progression of CRC.
This study showed an interaction between oral bacteria, lifestyle factors and genetic polymorphisms on the risk of oral cancer. The results also provided biological support for the established ...association between poor oral hygiene and oral cancer risk.
Abstract
Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1β, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.
•A phosphaphenanthrene/benzimidazolone-containing flame retardant (POBDBI) was synthesized successfully.•POBDBI imparted excellent flame retardancy and smoke suppression to EP.•POBDBI exerted ...flame-retardant effect both in condensed phase and gaseous phase.
A novel flame retardant POBDBI was generated by the reaction of p-dibenzaldehyde, 5-amino-2-benzimidazolinone and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), and employed to epoxy resin. The structure of POBDBI was measured by FT-IR and NMR tests. Then flame-retardant EP was fabricated by using POBDBI as a flame-retardant. The thermal stability, flame-retardant performance and fire behavior were investigated by a serious of comprehensive instruments. Combustion tests show the flame-retardant performance of composite materials has been significantly improved. For example, the EP/POBDBI-1.0 with the phosphorus content of 1.0% accorded a V-0 rating and its limiting oxygen index (LOI) value increased to 36.5%. Besides, total smoke production (TSP), peak heat release rate (PHRR) and total heat release (THR) of EP/POBDBI-1.0 dropped significantly, and the corresponding values were decreased by 48.4%, 48.9% and 8.7%, respectively. At the same time, the composition, morphology of chars and gaseous products of POBDBI were studied by X-ray photoelectron spectroscopy (XPS), FT-IR, scanning electron microscope (SEM) and Py-GC/MS. These results presented that POBDBI could not only exerted free radical capture effect, but also enhanced the density of char residue.
A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized via enantioconvergent dehydrative nucleophilic ...substitution. A broad range of 3,3′-, 3,2′- and 3,1′-BIMs were obtained under mild conditions with excellent efficiency and enantioselectivity (80 examples, up to 98% yield and >99 : 1 er). By utilizing racemic 3-indolyl tertiary alcohols as precursors of alkyl electrophiles and indoles as C–H nucleophiles, this organocatalytic strategy avoids pre-activation of substrates and produces water as the only by-product. Mechanistic studies suggest a formal SN1-type pathway enabled by chiral phosphoric acid catalysis. The practicability of the obtained enantioenriched BIMs was further demonstrated by versatile transformation and high antimicrobial activities (3al, MIC: 1 μg mL−1).
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