EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47.

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models. RESULTS: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models. CONCLUSIONS: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC.

Ambroxol for the treatment of COVID-19 among hospitalized patients: A multicenter retrospective cohort study.

Ambroxol is a commonly used mucolytic agent principally used to treat respiratory diseases, which may have a role as adjunctive therapy for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but there is lack of evidence about its effectiveness on coronavirus disease-2019 (COVID-19) patients. To study the association between ambroxol use and clinical outcomes among hospitalized patients of COVID-19 infection. We conducted a multicenter retrospective cohort study involving 3,111 patients with confirmed SARS-CoV-2 infection from three hospitals in Wuhan from 19 December 2019 to 15 April 2020, and the primary outcome was in-hospital mortality. COVID-19 patients were classified into ambroxol and non-ambroxol groups based on the administration of ambroxol during hospitalization. Two analyses including propensity score matching (PSM) to obtain a 1:1 balanced cohort and logistic regression were used to control for confounding factors. The average age of 3,111 patients was 57.55 ± 14.93 years old, 127 of them died during hospitalization, and 924 of them used ambroxol. Treatment with ambroxol did not have a significant effect on in-hospital mortality of COVID-19 patients when compared with non-ambroxol in PSM model after adjusting for confounders (8.0% vs. 3.5%, adjusted OR, 1.03 [95% CI, 0.54-1.97], p = 0.936). Adverse events such as nausea/vomiting, headache, and rash were comparable between the two groups. Our results suggest that the use of ambroxol is not significantly associated with in-hospital mortality in COVID-19 patients, which provides evidence for evaluating the effects of ambroxol on COVID-19 patient outcomes and may be helpful for physicians considering medication alternatives for COVID-19 patients.

Experience in management of cesarean scar pregnancy and outcomes in a single center.

OBJECTIVE: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features. METHODS: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding. RESULTS: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma. CONCLUSIONS: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.

Voriconazole-induced severe skin allergy and neurological adverse event in a liver failure patient: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. CASE SUMMARY: A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration.

Fluoride-bridged dinuclear dysprosium complex showing single-molecule magnetic behavior: supramolecular approach to isolate magnetic molecules.

Using Na-encapsulated benzo[18]crown-6 (Na)(B18C6) as a counter cation, we successfully magnetically isolated a fluoride-bridging Dy dinuclear complex {[(PW11O39)Dy(H2O)2]2F} (Dy2POM) with lacunary Keggin ligands. (Na)(B18C6) formed two types of tetramers through C-H⋯O, π⋯π and C-H⋯π interactions, and each tetramer aligned in one dimension along the c-axis to form two types of channels. One channel was partially penetrated by a supramolecular cation from the ±a-axis direction, dividing the channel in the form of a "bamboo node". Dy2POM was spatially divided by this "bamboo node," which magnetically isolated one portion from the other. The temperature dependence of the magnetic susceptibility indicated a weak ferromagnetic interaction between the Dy ions bridged by fluoride. Dy2POM exhibited the magnetic relaxation characteristics of a single-molecule magnet, including the dependence of AC magnetic susceptibility on temperature and frequency. Magnetic relaxation can be described by the combination of thermally active Orbach and temperature-independent quantum tunneling processes. The application of a static magnetic field effectively suppressed the relaxation due to quantum tunneling.

Factors affecting transtemporal window quality in transcranial sonography.

OBJECTIVE: To assess the influencing factors of transtemporal window quality and identify patients suitable for transcranial sonography (TCS) examination in two-dimensional imaging. METHODS: In this cross-sectional study, TCS was performed in 161 consecutive patients through the temporal bone window (TBW) in the neurology or neurosurgery department. Each patient's sex, age, height, weight, and temporal bone thickness (TBT) were collected. After examination, the patients were divided into two groups: TBW success and TBW failure. The data were statistically compared between the two groups. RESULTS: Among the studied population, the total TBW success rate was 80.1% (95% confidence interval [CI]: 74-86). The TBW success rate was 91.4% (95% CI: 85-98) in males and 70.9% (95% CI: 61-81) in females (p = .001). Sex (p = .001), age (p = .002), height (p = .047), and TBT (p < .001) showed significant differences between the TBW success and failure groups. In males, only TBT (p = .001) showed a significant difference; in females, age (p < .001) and TBT (p = .003) showed a significant difference. The area under the receiver operating characteristic curve (AUC) of sex, age, and TBT and their combination was 0.686, 0.659, 0.842, and 0.922 (p < .001), respectively. The AUC of the combination of parameters was significantly greater than that of age and sex alone (p = .007; p = .0002) but not greater than that of TBT (p = .090). CONCLUSIONS: The TBW success rate varied with sex, age, height, and TBT. Males, younger patients, taller patients, and patients with a thinner temporal bone tended to be more suitable for the examination by TCS.

Hepatic paraoxonase 1 ameliorates dysfunctional high-density lipoprotein and atherosclerosis in scavenger receptor class B type I deficient mice.

BACKGROUND: High-density lipoprotein (HDL) plays an antiatherogenic role by mediating reverse cholesterol transport (RCT), antioxidation, anti-inflammation, and endothelial cell protection. Recently, series of evidence have shown that HDL can also convert to proatherogenic HDL under certain circumstances. Plasma paraoxonase 1 (PON1) as an HDL-bound esterase, is responsible for most of the antioxidant properties of HDL. However, whether PON1 can serve as a therapeutic target of dysfunctional HDL-related atherosclerosis remains unclear. METHODS: In this study, scavenger receptor class B type I deficient (Scarb1-/- ) mice were used as the animal model with dysfunctional HDL and increased atherosclerotic susceptibility. Hepatic PON1 overexpression and secretion into circulation were achieved by lentivirus injection through the tail vein. We monitored plasma lipids levels and lipoprotein profiles in Scarb1-/- mice, and measured the levels and activities of proteins associated with HDL function. Meanwhile, lipid deposition in the liver and atherosclerotic lesions was quantified. Hepatic genes relevant to HDL metabolism and inflammation were analyzed. RESULTS: The results showed the relative levels of PON1 in liver and plasma were increased by 1.1-fold and 1.6-fold, respectively, and mean plasma PON1 activity was increased by 63%. High-level PON1 increased the antioxidative and anti-inflammatory properties, promoted HDL maturation and macrophage cholesterol efflux through increasing HDL functional proteins components apolipoprotein A1 (APOA1), apolipoprotein E (APOE), and lecithin-cholesterol acyltransferase (LCAT), while decreased inflammatory protein markers, such as serum amyloid A (SAA), apolipoprotein A4 (APOA4) and alpha 1 antitrypsin (A1AT). Furthermore, hepatic PON1 overexpression linked the effects of antioxidation and anti-inflammation with HDL metabolism regulation mainly through up-regulating liver X receptor alpha (LXRα) and its downstream genes. The pleiotropic effects involved promoting HDL biogenesis by raising the level of APOA1, increasing cholesterol uptake by the liver through the APOE-low density lipoprotein receptor (LDLR) pathway, and increasing cholesterol excretion into the bile, thereby reducing hepatic steatosis and aorta atherosclerosis in Western diet-fed mice. CONCLUSIONS: Our study reveals that high-level PON1 improved dysfunctional HDL and alleviated the development of atherosclerosis in Scarb1-/- mice. It is suggested that PON1 represents a promising target of HDL-based therapeutic strategy for HDL-related atherosclerotic cardiovascular disease.

Modulation of the properties of dinuclear lanthanide complexes through utilizing different ß-diketonate co-ligands: near-infrared luminescence and magnetization dynamics.

A family of new dinuclear lanthanide complexes as the simplest entities showing intramolecular magnetic interactions, [Ln2(dbm)2(L)2(CH3OH)2] (Ln = Tb (1), Dy (2), Ho (3), Er (4), Yb (5), Lu (6)), [Ln2(acac)2(L)2(EtOH)2] (Ln = Dy (7), Er (8)), [Dy2(TTA)2(L)2(CH3OH)2]·2CH2Cl2 (9) and [Dy2(tfa)2(L)2(CH3OH)2] (10) (H2L = N'-(2-hydroxy-5-methylphenyl)-pyrazine-2-carbohydrazide, Hdbm = 1,3-diphenyl-1,3-propanedione, Hacac = acetylacetone, HTTA = 2-thenoyltrifluoroacetone, Htfa = trifluoroacetylacetone), were constructed successfully by the reaction of a Schiff base ligand H2L and four different ß-diketonate salts. As for complexes 4, 5 and 8, all exhibit the characteristic emission peaks of the corresponding Er3+, Yb3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (510 nm) of 5 is located in the visible region, confirming its significant potential application value. Magnetic studies indicate that complexes 9 and 10 exhibit characteristic slow relaxation of magnetization with the energy barriers (Ueff) of 102 K for 9 and 140 K for 10 under a zero dc field. Under the optimized dc fields, slow magnetic relaxations are present in 2 and 7, and the Ueff values of 9 and 10 have been improved. This proves that the ß-diketonate co-ligands deserve an important role in regulating Dy-SMMs influenced by the diverse perturbations of the axial crystal field originating from minor changes in the coordination environment.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Using Real-Time Fusion Imaging Constructed from Contrast-Enhanced Ultrasonography and Magnetic Resonance Imaging for High-Grade Glioma in Neurosurgery.

OBJECTIVE: To compare the observation of high-grade glioma (HGG) based on intraoperative multiplane ultrasonography (US) images and preoperative reconstructive coplanar T1-weighted enhanced magnetic resonance imaging (MRI) using volume navigation (V Nav) fusion image technology. METHODS: We retrospectively evaluated intraoperative data obtained from 16 patients diagnosed with HGG (grade III and IV). Overall, 18 nodules observed in 15 patients were examined. HGG images from US and contrast-enhanced US (CEUS) were compared with those from preoperative reconstructive coplanar enhanced T1-weighted MRI using automatic V Nav fusion image technology. RESULTS: All HGG tumors were detected. Images of 13 of 18 tumors (72.2%) with obscure margins using B-mode US were improved with clear tumor boundaries using CEUS imaging. The relative difference in tumor area between CEUS and enhanced MRI modalities in 14 mainly solid component lesions was considered statistically significant (P value < 0.05). There was a perfect correlation of the enhanced area between coplanar CEUS and enhanced MRI. CONCLUSIONS: The V Nav fusion image system combining intraoperative real-time US imaging with reconstructive preoperative coplanar MRI is valuable for image-guided HGG resection. It is suitable for neurosurgeons who lack the expertise in US technology to discern the brain structure and allows better recognition of tumor and edema tissues compared with reconstructive preoperative coplanar-enhanced MRI in real time and in multiplane from different angles. In addition, CEUS combined with B-mode US could improve tumor detection and resection control in neurosurgery, even in single US-guided operations.

A new family of dinuclear lanthanide complexes constructed from an 8-hydroxyquinoline Schiff base and ß-diketone: magnetic properties and near-infrared luminescence.

Six phenoxo-O bridged dinuclear lanthanide(iii) complexes have been assembled utilizing the 2-[(4-nitrophenyl)imino]methyl-8-hydroxyquinoline (HL) and dibenzoylmethane (Hdbm) ligands: [Ln2(dbm)4L2] (Ln = Nd (1), Eu (2), Gd (3), Tb (4), Dy (5) and Er (6)). Complexes 1 and 6 exhibit the characteristic emission peaks of the corresponding Nd3+ and Er3+ ions, respectively. Meanwhile, the excitation wavelength (470 nm) for complex 1 is located in the visible-light region, confirming a practical application value. The studies on magnetic properties reveal that complex 3 features a magnetocaloric effect with a magnetic entropy change of -ΔSm = 14.36 J kg-1 K-1 at 4 K for ΔH = 7 T. What's more, the dynamic magnetic studies for complex 5 show that it exhibits slow magnetic relaxation behavior, typical of SMM behavior, resulting in an energy barrier of ΔE/kB = 75 K with the pre-exponential factor τ0 = 2.2 × 10-7 s. Meanwhile, this research demonstrates that the magnetic properties can be modulated by regulating the electron-donating/withdrawing effects of the substituents on the ligands.

The real-time ultrasonography for fusion image in glioma neurosugery.

OBJECTIVES: The aim of study is to evaluate the general performance and efficiency of the using real time intraoperative ultrasound system with Volume Navigation system technology in glioma. Compare glioma intraoperative ultrasound and contrast agent ultrasound images to obtained preoperative MRI with fusion image in a real-time. PATIENTS AND METHODS: Fifteen patients had been performed fusion imaging involved intraoperative real-time ultrasound and contrast agent ultrasound with preoperative MR imaging including preoperative gadolinium-enhanced MRI from March 2017 to December 2017. The number of tumor was counted online fusion imaging in real time ultrasound with and without preoperative MR. We analyzed ultrasound coplanar MR modalities in real time including tumor location, margin (obscure or defined). In addition, intraoperative ultrasound enhancement pattern was analyzed compare it to preoperative reconstruction gadolinium-enhanced T1-weighted MRI. Two radiologists who made planning ultrasound assessment for the focus lesion based on a 4 scoring system according to the degree of confidence. RESULTS: Thirteen of fifteen patients whose automatically registration successful intraoperative neurosurgery accepted preoperative MR examination. Seven of fifteen fine-tuning registration phase were performed and satisfactory with fusion image substantially. Intraoperatively, 73.3% (11/15) glioma nodules were definite on conventional B-mode US by a radiologist who doesn't know the MR result before fusion US with MRI. However, 100% tumors were detected on fusion B-mode ultrasound imaging with MRI. Two radiologists evaluated the score between fusion B-mode ultrasound and CEUS with coplanar MRI and had a result that score was upgraded in 69.2% (9/13) and 84.6% (11/13) patients. Inter-observer agreement was significant (kappa value = 1.0, p < 0.001) in B-mode ultrasound fusion image with MRI. Inter-observer agreement was moderate (kappa value = 0. 0.618, p < 0.001) in CEUS fusion image with MRI. CONCLUSION: Fusion imaging is very useful to detect poor sonographic visibility tumor on fusion B-mode US imaging with MR images. Fusion image may demonstrate multiplane images including same standard and nonstandard MRI and US images to help localize tumor. The additional real time fusion CEUS mode image with MR is a safe method for neurosurgery and the use of CEUS should be considered when fusion B-mode ultrasound imaging alone is not satisfactory for margin.

Pioglitazone attenuates aging-related disorders in aged apolipoprotein E deficient mice.

Pioglitazone (Piog) activates peroxisome proliferator activated receptor-γ (PPARγ) and is widely used in clinic for the treatment of diabetes mellitus. PPARγ in various tissues has the essential regulatory role of multiple metabolic function, suggest that PPARγ signaling may contribute to aging processes. However, little is known about the consequences of Piog on aging in aged animal models. We used apolipoprotein E deficient (apoE-/-) mice model to evaluate the effects of Piog on aging-related disorders. Our results showed that long-term and low-dose Piog treatment significantly reduced aortic atherosclerosis, aging-related renal glomerulosclerosis and interstitial fibrosis, and hepatic steatosis, while improved the dermis in skin atrophy, compared to the control group. These morphological alterations were linked to the role of Piog, including regulation of plasma cholesterol and triglycerides (TG) levels, increased antioxidant superoxide dismutase (SOD) activity and decreased myeloperoxidase (MPO) activity. Moreover, accompanied with up-regulation of PPARγ expression, Piog had obviously increased the mRNA levels of anti-aging genes Sirtuin1 and Klotho, decreased the p53 protein level, and altered the expression of several genes involving cholesterol excretion, TG biosynthesis and inflammation in the liver. In conclusion, Piog treatment is effective to modulate the oxidative and inflammatory status, cell senescence, and lipid metabolism, contributing to attenuate several aging-related disorders in the aged apoE-/- mice, thereby maybe a promising protective therapy of aging and age-related diseases.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats.

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and ß cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced ß cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic ß mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of ß cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

An intergenerational effect of neuroendocrine metabolic programming alteration induced by prenatal ethanol exposure in rats.

Prenatal ethanol exposure (PEE) induces hypothalamic-pituitary-adrenal (HPA) axis-related neuroendocrine metabolic programming alteration in the first generation (F1) rats. In this study, the HPA hormones and glucose/lipid phenotypes under basal state and stressed condition induced by a fortnight ice-water swimming were examined in F2 to verify the intergenerational effect. Under the basal state, serum corticosterone (CORT) and glucose of some PEE groups were lowered while those of serum triglycerides (TG) were increased comparing with controls. Following chronic stress, the percentage increase in CORT from the basal state tended to be greater for some PEE groups compared with controls while the percentage reduction of glucose and percentage elevation of TG were smaller. These results revealed that the low basal activity and hyper-responsiveness of the HPA axis as well as glucocorticoid-associated glucose and lipid phenotypic alterations were partially retained in F2, which indicates PEE-induced neuroendocrine metabolic programming alteration may have an intergenerational effect.

Color Doppler Ultrasound in Diagnosis and Assessment of Carotid Body Tumors: Comparison with Computed Tomography Angiography.

A carotid body tumor (CBT) is a rare, non-chromaffin paraganglioma, and its diagnosis mainly depends on imaging modalities. The aim of this study was to investigate the ability of color Doppler ultrasound (CDU) in the diagnosis and assessment of CBT based on computed tomography (CT). We retrospectively reviewed the CDU and CT features of 49 consecutive CBTs and 23 schwannomas from 67 patients and compared these findings with surgical resection specimens. The mean size of CBT lesions on ultrasound scans and CT angiography (CTA) was 3.24 cm ± 0.82 cm (range, 1.6-5.2 cm) and 3.84 cm ± 1.08 cm (range, 1.8-6.8 cm), respectively, which had statistically significant difference (t = 9.815, p = 0.000). The vascularity of CBT lesions was richer than that of schwannoma lesions (p < 0.05). Intra-lesional vascularities feeding CBT mostly arose from the external carotid artery and had spectrum characteristics including low velocity and resistance. Peak systolic velocity (PSV) and resistance index (RI) of the vasa vasorum were 39.8 cm/s ± 19.8 cm/s and 0.54 ± 0.06, respectively. There was the correlation between CTA and CDU in identifying Shamblin type I CBT lesions, while CTA technique was superior for CDU, identifying Shamblin type II and III CBT lesions. Accuracy, specificity and sensitivity of CDU in diagnosing CBTs were 87.5% (63 of 72), 82.6% (19 of 23) and 89.8% (44 of 49), respectively. Both accuracy and sensitivity of CTA in diagnosing CBTs were 100%. CDU can be useful for assessment of Shamblin's type and intra-lesional blood flow of CBTs before its metastases, while CT imaging can reveal the relationship between lesions and adjacent arteries, as well as the involvement of the skull base. CDU combined with CT imaging can be used as an optimal detection modality for the assessment and management of CBT.

Berberine hydrochloride impact on physiological processes and modulation of twist levels in nasopharyngeal carcinoma CNE-1 cells.

OBJECTIVE: The main purpose of this work was to investigate the effect of berberine hydrochloride (BH) on the proliferation, apoptosis, migration, and invasion of CNE-1 nasopharyngeal carcinoma cells. Our results shed light on the functional components of traditional Chinese herbs for potential use in modern medicine. METHODS: The CNE-1 cell line was treated with different concentrations of BH and effects on cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Anti-migratory and anti-invasive actions of BH were investigated using wound healing assays and the Millicell Hanging cell culture insert system, respectively. Expression of the epithelial-mesenchymal transition (EMT)-related gene twist (Twist) was analyzed by real-time PCR and Western blotting. Apoptosis was estimated with an annexin-V fluorescein (FITC) apoptosis detection kit, as well as with reference to levels of activated caspase-3 of CNE-1 cells before and after treatment with BH utilizing fluorescence spectroscopy. RESULTS: BH was capable of reducing proliferation and viability of CNE-1 cells in a dose- and time-dependent manner, also demonstrating anti-migratory and anti-invasive capacities which correlated with reduction in expression of Twist. Finally, BH was able to induce significant amounts of apoptosis in CNE-1 cells, as demonstrated by an increase in the activity of caspase-3 and in annexin-V staining following treatment. CONCLUSION: BH extracted from rhizoma coptidis demonstrated an ability to block proliferation, induce apoptosis, and impair the migration and invasion of the CNE-1 cell line Considering these properties, our results suggest that BH could be an important compound for consideration in the treatment of nasopharyngeal carcinoma.

Inhibition of endoplasmic reticulum stress and atherosclerosis by 2-aminopurine in apolipoprotein e-deficient mice.

We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE (-/-) ) mice, so called E(-)/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E(-)/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in apoE (-/-) mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in apoE (-/-) mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated apoE (-/-) mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control apoE (-/-) mice. In addition, the 2-AP-treated apoE (-/-) mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2 α in their aortic samples as compared to levels in untreated control apoE (-/-) mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in apoE (-/-) mice and that therapeutic strategies can be developed for using eIF-2 α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis.