MRCP Combined With CT Promotes the Differentiation of Benign and Malignant Distal Bile Duct Strictures.

OBJECTIVE: To determine whether contrast-enhanced computed tomography (CT) can promote the identification of malignant and benign distal biliary strictures (DBSs) compared to the use of magnetic resonance cholangiopancreatography (MRCP) alone and to identify imaging findings of malignant DBSs. MATERIALS AND METHODS: A total of 168 consecutive patients with confirmed DBSs were reviewed. MRCP alone and MRCP combined with CT images were blindly analyzed by two radiologists (e.g., stricture pattern, margins), and malignant or benign DBSs were identified based on surgical findings, endoscopy findings, or follow-up. The diagnostic accuracy of the two reviewers using MRCP alone and MRCP combined with CT were evaluated. MRCP and CT features of malignant and benign DBSs were compared using multiple logistic regression analysis to identify independent malignant risk factors. RESULTS: MRCP combined with CT examination could improve the diagnostic accuracy, which increased from 70.2% to 81.5% in Doctor A and from 85.1% to 89.3% in Doctor B. The multiple logistic regression model revealed that stricture length [odds ratio (OR) 1.070, P=0.016], angle of the DBS (OR 1.061, P<0.001), double duct sign (OR 4.312, P=0.003) and low density in the arterial phase (OR 0.319, P=0.018) were associated with malignant DBS. A scoring model incorporating these four factors was established; at a threshold value of 1.75, and the sensitivity and specificity for the detection of malignant DBSs were 73.5 and 85.9%, respectively. CONCLUSIONS: Compared to the use of MRCP alone, MRCP combined with contrast-enhanced CT can improve the accuracy of DBS diagnosis. The scoring model accurately predicts malignant DBSs and helps make treatment decisions.

Discrimination of serous cystadenoma from mucinous cystic neoplasm and branch duct intraductal papillary mucinous neoplasm in the pancreas with CT.

PURPOSE: The imaging features of serous cystadenomas (SCAs) overlap with those of mucinous cystic neoplasms (MCNs) and branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), and an accurate preoperative diagnosis is important for clinical treatment due to their different biological behaviors. The aim of this study was to provide a computed tomographic (CT) feature for the diagnosis of SCAs and estimate whether the "circumvascular sign" can contribute to the discrimination of SCAs from MCNs and BD-IPMNs. METHODS: From August 2011 through December 2019, a total of 71 patients (30 patients with 30 SCAs, 21 patients with 21 MCNs and 20 patients with 22 BP-IPMNs) were enrolled in this study. All patients underwent CT examination and were confirmed by surgical pathology. In addition to patient clinical information, CT features (e.g., location, shape) were evaluated via CT. RESULTS: Central scarring, central calcification and the circumvascular sign were found to be specific CT features for the diagnosis of SCAs and their differential diagnosis from MCNs and BD-IPMNs. All three CT features had high specificity, and both central scarring and central calcification had low sensitivity. When any one of these two features was combined with the circumvascular sign, the sensitivity increased to 83.3%. CONCLUSION: Pancreatic cystic neoplasms that show central scarring, central calcification or the circumvascular sign on CT could be diagnosed as SCAs. When either of the first two features is combined with the circumvascular sign, the diagnostic sensitivity could be increased.

SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis.

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K-AKT. SKA3 was also found to bind and activate EGFR to activate PI3K-AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K-AKT signaling.

Experimental and theoretical validations of a one-pot sequential sensing of Hg2+ and biothiols by a 3D Cu-based zwitterionic metal-organic framework.

A zwitterionic three-dimensional (3D) metal-organic framework (MOF) of {[Cu(Cdcbp)(bipy)]·4H2O}n (1) has been synthesized and characterized (H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide; bipy = 4,4'-bipyridine). MOF 1 exhibits a variety of structural traits, such as ligand conjugated, positively charged pyridinium center, and Cu(II) cations that collectively enable its efficient hybridization with the flexible, negatively charged, single-stranded, and thymine-rich (T-rich) DNA. The T-rich DNA is labeled with carboxyfluorescein (FAM) fluorescent probe (characterized as P-DNA), but the resultant MOF 1 - P-DNA hybrid (characterized as P-DNA@1) is non-emissive (off-state) because of the fluorescent quenching by MOF 1. The P-DNA@1 hybrid functions as an effective and selective sensor for Hg2+ due to the formation of rigid hairpin-like T-Hg2+-T double-stranded DNA (ds-DNA@Hg2+) which is subsequently ejected by MOF 1, triggering a recovery of the P-DNA fluorescence (on-state). Subsequent addition of biothiols further sequestrates Hg2+ from the ds-DNA@Hg2+ duplex driven by the stronger Hg-S coordination, thus release the P-DNA and, in turn, resorbed by MOF 1 to regain the initial hybrid (off-state). P-DNA@1 hybrid thus detects Hg2+ and biothiols sequentially via a fluorescence "off-on-off" mechanism. The limits of detection (LOD) for Hg2+, biothiols, including cysteine (Cys), glutathione (GSH) and homocysteine (Hcy) are 3.0, 14.2, 15.1 and 8.0 nM, respectively, with the detection time of 60 min for Hg2+, and instantaneous detection for all the three biothiols. The detection mechanism is further confirmed by circular dichroism (CD), fluorescence anisotropy (FA), binding constant and molecular simulation. This sequential detection of Hg2+ and biothiols counter-proofs the presence of each other and may shed light to the occurrence of related diseases, such as neurodegenerative disorders of Parkinson's disease (PD), and Alzheimer's disease (AD).

Associations between human aldosterone synthase CYP11B2 (-344T/C) gene polymorphism and antihypertensive response to valsartan in Chinese patients with essential hypertension.

Aldosterone synthase is a mitochondrial enzyme that catalyzes the conversion of 11-deoxycorticosterone to the potent mineralocorticoid aldosterone. The gene encoding aldosterone synthase, CYP11B2, is associated with essential hypertension. But if the genetic variations in aldosterone synthesis could influence the antihypertensive response to Valsartan is not clear. A Chinese sample of 502 persons (217 women) was studied, which was divided into the hypertensive group (EH) of 345 persons and the normotensive group (NB) of 157 persons. Subjects were genotyped through the use of the polymerase chain reaction for the diallelic polymorphisms in CYP11B2. 98 persons of the essential hypertension group received 4 weeks therapy with valsartan. Blood pressure, 24-hour ambulatory blood pressure, biochemical index were also determined. The frequency of CC+CT genotypes in hypertensive group was significantly higher than that in normotensive group (P<0.05), the frequency of C allele of gene CYP11B2 (-344T/C) in hypertensive group was significantly higher than that in normotensive group (P<0.01). The descending values of SBP (systolic blood pressure), DBP (diastolic blood pressure), MAP (mean arterial pressure), 24 h SBP (mean SBP of 24 hours), 24 h DBP (mean DBP of 24 hours), 24 h MAP (mean arterial pressure of 24 hours) of CC+CT genotype group were significantly higher than those of the TT genotype group (P<0.05). The aldosterone synthase CYP11B2 (-344T/C) gene polymorphism is associated with essential hypertension in Chinese. And the aldosterone synthase CYP11B2 (-344T/C) gene polymorphism may be the predictor of the antihypertensive response to Valsartan.

[Epithelial-mesenchymal transition induces cancer stem cell generation in human thyroid cancer cells in vitro].

OBJECTIVE: Epithelial-mesenchymal transition (EMT) has been implicated in the initiation and conversion of early stage tumors into invasive malignancies and is associated with the "stemness" of cancer cells. The present study was designed to identify whether EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. METHODS: FTC133 cells, as EMT-negative cells, were used for EMT induction by hypoxia-inducible factor-1α (HIF-1α) transfection. And EMT features were then examined by Western blot, immunofluorescent staining, invasion and proliferation assays. Moreover, stem-like side population (SP) cells were sorted with flow cytometry from FTC133 cells before and after EMT. The proportion of SP was compared and stemness, self-renewal and tumorigenicity in vitro were identified in SP cells. RESULTS: Overexpression of HIF-1α induced FTC133 cells to undergo EMT. And it down-regulated epithelial marker E-cadherin, up-regulated mesenchymal marker vimentin and caused nucleus translocation of ß-catenin and highly invasive and metastatic properties. Most importantly, the induction of EMT promoted proportion of stem-like side population cells (0.70% vs 0.03%, P < 0.05) with higher sphere formation and clone forming capability in contrast to non-side population cells. CONCLUSIONS: EMT can induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding the role of EMT and cancer stem cells in cancer progression may reveal new preventive and therapeutic targets for thyroid cancers.

Epithelial-mesenchymal transition triggers cancer stem cell generation in human thyroid cancer cells.

Increasing evidence has shown that cancer stem cells or tumor initiating cells are the 'root cause' of malignant cancers. However, the exact origin of cancer stem cells still remains obscure in thyroid research. EMT has been implicated in the initiation and conversion of early-stage tumors into invasive malignancies and is associated with the stemness of cancer cells. Based on these facts, a new hypothesis was suggested that EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. In the present study, FTC133 cells identified as EMT-negative cells were used for EMT induction by HIF­1α transfection. Overexpression of HIF-1α induced FTC133 cells to undergo EMT, downregulated the epithelial markers E-cadherin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Most importantly, the induction of EMT promoted the stem-like side population cell proportion in the FTC133 cells. These results indicate that EMT induction promotes CSC traits and cell proportions in the thyroid cancer cells, which implies that EMT could induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding of the role of EMT and cancer stem cells in cancer progression may reveal new targets for the prevention or therapy of thyroid cancers.

Impact of diabetes on the prognosis of hip fracture: a cohort study in the Chinese population.

BACKGROUND: Diabetes has been associated with increased risk of fracture and impaired fracture healing. The aim of this study was to examine the influence of diabetes on perioperative complications, length of stay and ambulatory ability recovery in individuals with hip fracture, and to determine whether changes could be made to improve treatment outcome. METHODS: The study included 707 hip fracture patients treated at Beijing Jishuitan Hospital between July 2009 and December 2010. The medical history and perioperative complications were compared between non-diabetic and diabetic groups. Length of stay, days awaiting surgery, and days of hospitalization after surgery were also analyzed. Ambulatory ability was compared at 1-year follow-up using the Chi-square test and Fisher's exact test. An independent Student's t-test was used to compare normally distributed continuous data. RESULTS: Patients with diabetes were more likely than non-diabetic patients to develop cardiac perioperative complications (8.9% vs. 3.0%, P = 0.021), urinary tract infections (12.0% vs. 2.8%, P < 0.001), and gastrointestinal symptoms (15.0% vs. 6.8%, P = 0.003). No difference in perioperative complications was observed between the groups. Days awaiting surgery and length of hospital stay were both longer in the diabetic group ((8.0 ± 5.1) vs. (6.2 ± 3.7) days and (16.5 ± 3.8) vs. (13.3 ± 3.8) days, P < 0.001, respectively). Before the occurrence of fracture, patients with diabetes were less likely to be ambulatory outdoors (71.9% vs. 85.9%, P < 0.001) and had more restricted walking ability. After at least 1-year follow-up, similar proportions of patients in the non-diabetic and diabetic groups (16.1% and 15.9%, respectively), who were able to ambulate outdoors before the fracture, became housebound till the final follow-up. CONCLUSIONS: Diabetics are at increased risk of specific complications and have a longer time to surgery and longer in-hospital stay, but generally have similar recovery to non-diabetics thereafter.

Prevalence of Osteoporosis and Its Associated Factors among Older Men with Type 2 Diabetes.

This study investigated the prevalence of osteoporosis and its associated factors in old men with T2DM to identify risk factors for low BMD. We enrolled 93 old men (≥60 years of age) with T2DM and 125 healthy old men (controls) and collected data of their lifestyle, medical history, bone densitometry, body weight, height, and blood pressure. Blood samples were collected for biochemical analyses. Urine samples were collected to determine 24 h urinary creatinine, albumin, and protein. Although no differences in age, blood pressure, waist-to-hip ratio, body mass index (BMI), and testosterone levels were observed, the prevalence of low BMD was significantly higher in the T2DM group compared to the control group. The risk of developing low BMD and fracture in T2DM subjects was increased by 46- and 26-fold, respectively, compared to control subjects. BMD of total spine and hip was positively correlated with BMI and negatively correlated with age, duration of diabetes, creatinine, and 24 h urinary albumin. So old men with T2DM have a greater risk of developing low BMD than old men without T2DM.

[Isolation, proliferation and differentiation of thyroid stem cell from human thyroid nodule tissue].

OBJECTIVE: To explore the presence of a characteristic stem cell population (side population, SP) in human thyroid gland and perform sphere culture method for the isolation and proliferation of thyroid stem cell. METHODS: Flow cytometry and cell sorting were performed to identify and isolate the ABCG2-positive SP cells from primary thyroid cells. The comparison of gene profiles and morphology between SP and main population (MP) were performed. Primary thyroid cells were also cultured in neurosphere-like growth condition for sphere formation. Gene profile of developed spheres was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and thyroid lineage commitment was then induced in a differentiating condition. In stem cell-derived thyrocytes, embedded in collagen to form follicles, TSH-dependent (125)iodide uptake was measured. RESULTS: The SP was identified as a population enriched in stem cells with typical morphology, and characteristics of self-renewal and differentiation. Nonadherent clonal spheres developed in thyroid cell cultures, displaying an expression pattern resembling that of SP cells and in response to TSH and serum these sphere cells differentiated into thyrocytes expressing PAX8, thyroglobulin, sodium iodide symporter, thyroid-stimulating hormone receptor and thyroperoxidase mRNA. And there was TSH-dependent (125)iodide uptake. CONCLUSION: It is shown first time that human thyroid contains an undescribed population of cells with SP phenotype and clonal expansion capacity. Moreover sphere culture method is developed for the isolation and proliferation of thyroid stem cell.

Electrochemiluminescence determination of codeine or morphine with an organically modified silicate film immobilizing Ru(bpy)3(2+).

An ECL approach was developed for the determination of codeine or morphine based on tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)(3)(2+)) immobilized in organically modified silicates (ORMOSILs). Tetramethoxysilane (TMOS) and dimethyldimethoxysilane (DiMe-DiMOS) were selected as co-precursors for ORMOSILs, which were then immobilized on a surface of glassy carbon electrode (GCE) by a dip-coating process. Ru(bpy)(3)(2+) was immobilized in the ORMOSIL film via ion-association with poly(p-styrenesulphonate). The ORMOSIL-modified GCE presented good electrochemical and photochemical activities. In a flow system, the eluted codeine or morphine was oxidized on the modified GCE and reacted with immobilized Ru(bpy)(3)(2+) at a potential of +1.20 V (vs. Ag/AgCl). The modified electrode was used for the ECL determination of codeine or morphine and showed high sensitivity. The calibration curves were linear in the range 2 x 10(-8)-5 x 10(-5) mol/L for codeine and 1 x 10(-7)-3 x 10(-4) mol/L for morphine. The detection limit was 5 x 10(-9) mol/L for codeine and 3 x 10(-8) mol/L for morphine, at signal:noise ratio (S:N)=3. Both codeine and morphine showed reproducibility with RSD values <2.5% at 1.0 x 10(-6) mol/L. Furthermore, the modified electrode immobilized Ru(bpy)(3)(2+) was applied to the ECL determination of codeine or morphine in incitant samples.

[Effect of E-selectin A561C (S128R) polymorphism on blood pressure].

OBJECTIVE: To investigate the effect of E-selectin A561C (S128R) polymorphism on blood pressure. METHODS: 347 essential hypertensive patients (male 163 and female 184, age 46.08 +/- 12.49 y, and body mass index 26.13 +/- 3.14 kg/m(2)) and 315 normal controls (male 93 and female 222, age 42.21 +/- 14.67 y, and body mass index 25.66 +/- 3.19 kg/m(2)) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Phenotypic measurements included blood pressure, blood glucose, serum triglycerides, serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, serum uric acid, blood urea nitrogen, nitric oxide, endothelin, angiotensin I, and II and plasma aldosterone. RESULTS: The frequencies of the AC and CC genotypes (6.92%) and C allele (4.76%) were significantly (P = 0.029 and 0.013) higher in hypertensive patients than normal controls (3.17% and 2.22%). The relative risk of hypertension associated with the C allele was 2.197 (95% CI: 1.164-4.144). Both diastolic blood pressure and mean arterial pressure were higher in C allele carriers than AA subjects (P = 0.049 and 0.024). Furthermore, C allele carriers, compared with AA subjects, had higher concentrations of blood glucose, and total and LDL cholesterol (P = 0.031, 0.046, and 0.003) and lower concentrations of nitric oxide (P = 0.036). CONCLUSION: The E-selectin A561C (S128R) polymorphism might affect blood pressure in Chinese.