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This study aimed to compare the effects of different hydrolysates (named GKOS and MKOS) on constipated rats, which were obtained by degradation from konjac glucomannan by β-glucanase and β-mannanase, respectively. GKOS and MKOS were characterized and administered by gavage at 100 mg kg

To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC.In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings.A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916.The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode.• In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

An intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic precursor lesion, and it often harbors mutations in KRAS, GNAS, and RNF43. To clarify the molecular profiles of IPMNs, we conducted mutation analysis of KRAS, GNAS, and RNF43 in 61 IPMN formalin-fixed, paraffin-embedded (FFPE) specimens. The mutation rates of codons 12, 13, and 61 in KRAS and codon 201 in GNAS were detected by Sanger sequencing. Next-generation sequencing was performed on RNF43, and the results were further verified by Sanger sequencing. We identified KRAS and GNAS mutations in 35 (57%) and 40 (66%) IPMN cases, respectively. GNAS mutations were significantly correlated with the morphologic subtype (P<0.001) and were more prevalent in the intestinal subtype (93%) than in the gastric (55%) and pancreatobiliary subtypes (44%) but were absent in the oncocytic subtype. RNF43 mutations were found in 5 cases (8%), all of which occurred in high-grade dysplasia and invasive lesions (2/5 and 3/5). All 5 cases harboring RNF43 mutations also exhibited GNAS mutations. RNF43 mutations were associated with a worse prognosis in invasive IPMN patients (P=0.002), while KRAS and GNAS mutations did not affect the prognosis of patients.

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD.

BACKGROUND: To investigate the prognostic value of a novel immune-inflammatory index, the interleukin-6-to-lymphocyte ratio (IL-6/LY), with the clinical outcomes of severe coronavirus disease 2019 (COVID-19) cases. METHODS: A cohort study of COVID-19 patients in Tongji Hospital, from January 2020 to February 2020, was evaluated. Kaplan-Meier method and the log-rank test was performed to analyze survival data. Univariate and multivariate analyses were performed with COX proportional hazard regression model. The primary and secondary outcomes were in-hospital mortality and multiple organ dysfunction syndrome (MODS), respectively. RESULTS: Total 320 adult patients were enrolled in our analyses. Patients were divided into low IL-6/LY group and high IL-6/LY group based on the cutoff value with 2.50. The Kaplan-Meier survival curves showed that high-value group (IL-6/LY ≥ 2.50) had a greater risk of poor prognosis (P

Background Our study aimed to investigate the prognostic value of a novel inflammatory index, systemic immune-inflammation index (SII), with the clinical outcomes of patients infected with coronavirus disease 2019 (COVID-19).Methods We evaluated a cohort study of COVID-19 patients (18–95 years old) in Tongji Hospital of Huazhong University of Science and Technology from January 28th 2020 to February 29th 2020. The enrolled patients were divided into two groups (including low-SII group and high-SII group) according to the cut-off point which is analyzed by receiver operating characteristic (ROC) curve. Univariate and multivariate COX regression analysis were performed to identify the factors associated with the outcomes of patients with COVID-19 infection. The primary and secondary outcome were in-hospital mortality and the development of acute respiratory distress syndrome (ARDS), respectively.Results A number of 326 adult patients (43.87% males, 61.22 ± 0.86 years) were enrolled in the final analyses. There were 147 cases (45.09%) died in hospital and 116 patients (35.58%) developed ARDS. ROC curve analysis indicated that the SII had a greater prediction accuracy in predicting the in-hospital mortality (area under the curve [AUC] = 0.789, sensitivity = 69.90%, specificity = 70.80%) and the development of ARDS (AUC = 0.736, sensitivity = 67.80%, specificity = 71.10%). Kaplan-Meier analysis revealed that patients in high-SII group had a greater risk of adverse clinical outcomes (all P P = 0.028) and the developed ARDS (HR = 6.832, 95%CI = 2.583–18.074, P

Acinar cell carcinoma of pancreas(ACCP)is a rare pancreatic exocrine tumor that accounts for about 1% of pancreatic tumors. The typical imaging manifestations of ACCP are as follows:(1)the tumor is large in volume,partially or completely exophytic;(2)complete or incomplete capsule is visible with thin linear enhancement;(3)CT density and MRI signal:plain CT images reveals that the tumors have similar or slightly hypodense densities relative to the adjacent normal pancreas,the solid part of ACCP has low to intermediate signal intensity on T1WI and intermediate to high signal intensity on T2WI compared with the surrounding normal pancreas;(4)pattern of enhancement:tumors exhibit heterogeneous enhancement and it is less than that in the surrounding normal pancreas;(5)fissure-like,swirling necrosis that may be a characteristic change of tumor;(6)pancreatic and biliary duct dilatation is rare;(7)adjacent organs and blood vessels around the pancreas may be invaded;(8)distant metastasis of liver and other parts may be observed;(9)PET-CT shows high FDG uptake. An ACCP patient with atypical imaging manifestations was treated in Peking Union Medical College Hospital from November 2015 to August 2017. The lesion manifested iso-enhancement and many imaging examinations failed to find the tumor. The patient ultimately underwent surgery and diagnosed as ACCP by pathology.

Intraductal papillary mucinous neoplasms of the pancreas (IPMN) are among the most important precancerous lesions in the pancreas. V-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most important genes involved in pancreatic neoplasms, and exhibits a high mutation rate in pancreatic ductal adenocarcinomas and pancreatic intraepithelial neoplasia. The present study aimed to further elucidate the associations among IPMN subtypes (gastric, intestinal, pancreatobiliary and oncocytic), pathological classifications [low-grade, intermediate-grade, and high-grade IPMN, and associated minimally invasive carcinoma (invasive depth ≤0.5 cm) and advanced invasive carcinoma (invasive depth >0.5 cm)]. A total of 56 cases of IPMN were studied using scorpion amplified refractory mutation system analysis of KRAS mutations, pathological features and prognosis. KRAS mutations were identified in 50% (28/56 cases). The frequency was 60% (9/15 cases) in gastric-type, 52.6% (10/19 cases) in intestinal-type, 47.3% (9/19 cases) in pancreatobiliary-type and zero (0/3 cases) in oncocytic-type IPMN. Except for oncocytic type IPMN, the frequencies of KRAS mutations in IPMN with low, intermediate and high grade, and IPMN-associated carcinoma were 58.3% (7/12 cases), 27.3% (3/11 cases), 80% (4/5 cases) and 56% (14/25 cases), respectively. With more advanced dysplasia and invasion, the prevalence of KRAS mutations in intestinal-type IPMN increased (P=0.012). The Kaplan-Meier survival curve demonstrated that survival rate was not associated with KRAS mutation (log-rank test; P=0.308). The prevalence of KRAS mutations was lowest in intestinal-type IPMN, and was in proportion to the degree of dysplasia and invasion. Therefore, KRAS mutation in IPMN does not correlate with histological subtype, dysplasia grade, depth of invasion or survival.

Objective To evaluate the clinical and pathologic characteristics of intraductal pancreatic neuroendocrine tumors (PanNETs). Methods Four cases of intraductal PanNETs were studied by light microscopy and immunohistochemistry with the analysis of morphologic features and review of relevant literatures. Results Two female patients and two male patients aged 41- 58 years were enrolled in this study. The chief complaint was abdominal pain in two patients,vomiting in one patient,and jaundice in the last patient. Imaging examination showed intraductal neoplasm with diagnosis as intraductal papillary mucinous neoplasm (IPMN) in case 1; space-occupying lesions were found in the head of pancreas in the other three cases with pancreatic ductal ectasia and distal pancreatic atrophy. Grossly the masses were located in pancreatic main duct and invaded into surrounding pancreatic parachyma. Microscopically the tumors arranged with solid pattern,with some trabecular structures in the last two cases. Small duct and ductules were seen in intraductal PanNETs. The immunohistochemical expression showed that SYN and CgA were positive in neoplastic cells and negative in small duct and ductules.Conclusions Intraductal PanNETs are rare conditions. The clinical symptoms and imaging findings are similar to IPMN or pancreatic carcinoma. The tumors are located within pancreatic duct partly and can invade the pancreatic parenchyma. Microscopically the neuroendocrine tumors mix with small duct and forms ductulo-insular structure,which should be differentiated with mixed ductal endocrine carcinoma. The grade and prognosis are similar to those of classical neuroendocrine tumors.

Objective The purpose of this study was to identify histopathologic correlates for the varied appearances of breast masses on contrast-enhanced ultrasonography (CEUS). Methods Contrast-enhanced ultrasonography was performed in 104 patients (age range, 19-86 years) after administration of a sulfur hexafluoride microbubble contrast agent, and enhancement patterns were classified as no enhancement, peripheral enhancement, homogeneous enhancement, regional enhancement, and heterogeneous enhancement. All patients' histologic slides were reviewed and correlated with CEUS findings. Results In malignant masses, heterogeneous enhancement corresponded to tumor cell cords or clusters in a variable amount of desmoplastic stroma. Homogeneous enhancement corresponded to hypercellularity in the whole mass, or ductal carcinoma in situ (DCIS) was predominant. Regional enhancement corresponded to a DCIS component. Peripheral enhancement corresponded to a DCIS component, hypercellularity or adenosis at the periphery, and low-degree cellularity, degeneration, fibrosis, or necrosis in the center. No enhancement was present in 1 case of low-grade DCIS. In benign masses, heterogeneous enhancement corresponded to loose cell proliferation in a more sclerotic stroma. Homogeneous enhancement corresponded to diffuse hypercellularity, an inflammatory cell infiltrate, or intraductal papilloma. Regional enhancement corresponded to focal hypercellularity or intraductal papilloma within a dilated duct. No enhancement corresponded to desmoplastic stroma. Peripheral enhancement was shown in 1 case of granulomatous mastitis with an inflammatory infiltrate at the periphery and necrosis in the center. Conclusions Breast mass CEUS findings correlated with histologic features.

Accurate assessment of tumor size is necessary when selecting patients for breast-conserving surgery. In the study of breast contrast-enhanced ultrasound (CEUS), we found that tumor size discrepancy between CEUS and conventional ultrasound (US) existed in some breast lesions, for which the reasons are not clear. Breast CEUS examinations were performed in 104 patients with breast lesions. The measurement of the 104 breast tumors on conventional US was obtained and compared with the measurement on CEUS. A difference in measuring tumor size of >3 mm for tumors up to 1.7 cm and 4 mm for tumors >or=1.7 cm, was defined as a significant discrepancy between conventional US and CEUS. The histopathological examination of size discrepancy was performed and the margin characteristics of breast cancers with larger measurements were compared with those with unchanged measurements. Among the 104 lesions (43 malignant, 60 benign, 1 borderline), the size of 27 breast cancers and one granulomatous mastitis appeared larger at CEUS. Pathologic examinations of the region corresponding to the measurement discrepancy were mainly ductal carcinomas in situ (DCIS), invasive carcinoma with a DCIS component, adenosis with lobular hyperplasia in breast cancers and inflammatory cell infiltration in one granulomatous mastitis. Well-defined margin characteristics were significantly different between breast cancers with larger measurements at CEUS and those with unchanged measurements of size (p = 0.002), whereas no significant difference was found between the two groups in ill-defined, spiculated, hyperechoic halo, microlobulated and angulated margins (p = 0.463, 0.117, 0.194, 0.666 and 0.780, respectively). This initial study suggests that significant discrepancy of breast lesion measurement between conventional US and CEUS is more likely presented in breast cancer than benign lesions. The pathologic findings corresponding to the region of size increased at CEUS are malignant in most malignant lesions and benign in benign lesions. It is difficult to predict whether the size measurement of the breast cancer increases at CEUS based on the margin characteristics showed on conventional US.

Large-cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare. We present a 63-year-old Chinese female who was admitted with right upper quadrant pain and a quasi-circular tumor measuring 2.0 cm on the body of the gallbladder, as indicated by computed tomography. LCNEC combined with adenocarcinoma was immunohistochemically confirmed after open radical cholecystectomy. Postoperative recovery of this patient was uneventful, and no evidence of recurrence or metastasis was observed after 12 months of follow-up. LCNEC of the gallbladder is thought to be extremely rare and is usually found in combination with other histological carcinoma types, such as adenocarcinoma, as determined histologically. The prognosis is poor overall, but early detection with complete resection may result in a relatively good prognosis.

Pure and carbon-containing olivine LiMn0.7Fe0.3O4 were synthesized at 600 °C by the method of solid-state reaction. Structure, surface morphology and charge/discharge performance of LiMn0.7Fe0.3O4 were characterized by X-ray diffraction, scanning electron microscopy, and electrochemical measurement, respectively. The prepared materials with and without carbon both show the single olivine structure. The morphologies of primary particles are greatly affected by the addition of carbon. Large particles (500–1000 nm) and densely sintered blocks were observed in pure LiMn0.7Fe0.3PO4, which made the insertion and extraction of lithium ions difficult. Battery made from this sample can not charge and discharge effectively. The carbon-containing LiMn0.7Fe0.3PO4 has a small particle size (100–200 nm) and a regular appearance. This material demonstrates high reversible capacity of about 120 mAh g−1, perfect cycling performance, and excellent rate capability. It is obvious that the addition of carbon plays an important role in restricting the particle size of the material, which helps to prepare LiMn0.7Fe0.3PO4 with excellent electrochemical performance. The electrochemical reaction resistance is much lower in the partly discharged state than in the fully charged or fully discharged state by the measurement of ac impedance for carbon-containing LiMn0.7Fe0.3PO4. It is indicated that the mixed-valence of Fe3+/Fe2+ or Mn3+/Mn2+ is beneficial to the transfer of electron which happens between the interface.

A new force field (MSXX FF) was developed for barium sulfate (BaSO_4) to reproduce the experimental properties of BaSO_4 crystal (density, lattice energy, compressibility, and vibrational spectrum) and to describe properly the interaction between BaSO_4 and water (binding energies and interatomic distances of Ba(H_2O)_8^(2+) and (SO_4)(H_2O)_6^(2-) clusters determined from ab initio quantum mechanics calculations). Using this FF in combination with F3C FF for water, the surface energies for several surfaces of BaSO_4 were examined both in a vacuum and in the presence of an explicit water bath in contact with them. The same level of FF's are also reported for CaSO_4 and SrSO_4.

The photodissociation of Na⋯FH van der Waals molecules in the 1.5–2.3 eV energy region is a very interesting system for transition state spectroscopy, because the potential energy surfaces for electronically excited states funnel the system down to the ground electronic state in a critical region where detailed features of the potential energy surfaces may be important in determining the branching probability between the harpooning reaction to form NaF or the dissociative E→V energy transfer process to form vibrationally excited HF. We used an analytic representation, reported earlier, of the potential surfaces for the two lowest A′ electronic states of NaFH as well as separable fits for two higher excited potential surfaces to simulate the experimental photodepletion spectrum of the Na⋯FH van der Waals molecule. Franck–Condon analysis was performed for the X 2A′→A 2A′, X 2A′→B 2A″, and X 2A′→B′ 2A′ transitions to predissociative states of the exciplex by making a separable approximation in Jacobi co...

High-level ab initio calculations of the ground and several excited-state adiabatic potential surfaces of the NaFH system are reported. These calculations were performed by multireference configuration interaction on a large grid of geometries which allowed them to be used for constructing an accurate analytic representation of the NaFH potential surfaces. For the ground and first excited states, using a genetic algorithm, an analytic 2×2 matrix fit was obtained corresponding to a diabatic representation. The off-diagonal coupling was obtained by fitting the energy gap between the surfaces in the region of their avoided crossing, and the diagonal elements were then fit to reproduce the ab initio adiabatic energy at 1530 points. The full fit was used to locate the barrier and the van der Waals well on the ground-state potential surface, the exciplex on the first-excited-state potential surface, and the minimum energy path for the ground-state Na+HF→NaF+H reaction. Additional calculations on the van der Waals and saddle point regions were carried out by a variety of ab initio methods as a check on accuracy. Major topological features of the potential energy surfaces representing higher-than-first excited states were examined.

To study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of intraductal tubulopapillary neoplasm of the pancreas (ITPN).The clinical findings, morphologic features, immunophenotype (by EnVision method) and KRAS gene alterations (by reverse transcriptase-polymerase chain reaction) of 6 cases of ITPN encountered during the period from January, 2001 to June, 2010 were analyzed.There were altogether 2 males and 4 females. The mean age of the patients was 64 years. Gross examination showed that the tumors were located in large pancreatic ducts and appeared as polypoid nodules with ductal obstruction. Solid tumor nodules associated with adjoining dilated ducts were identified in one case. Histologically, the tumors were characterized by tubulopapillary growth pattern without luminal mucin. The tumor cells showed high-grade nuclear atypia with scanty intracytoplasmic mucin. Intraductal necrotic foci were frequently observed. Immunohistochemical study showed that the tumor cells expressed CK7 and CK19. Focal positivity for MUC5AC was demonstrated. Two cases expressed MUC1. The staining for MUC2 was negative. KRAS gene mutations were identified in 2 cases, with a single-amino-acid substitution in codon 12 (35GA and 35GT/34GA).ITPN is a newly described pancreatic intraductal neoplasm and different from intraductal papillary mucinous neoplasm. ITPN is characterized by intraductal tubulopapillary growth pattern, severe cytologic atypia and scanty mucin secretion.

To investigate macroscopic performance and microcosmic ecosystem of CANON process in low ammonium concentration at room temprature, a steady-operation CANON reactor was achieved in different ammonium concentrations by adjusting aeration and hydraulic retention time (HRT), and the effect of ammonium concentration on the abundance and community structure of functional bacteria was analyzed using PCR-DGGE and real-time PCR. The results indicated a high TN removal loading of over 1.0 g.(L.d)-1 in relatively high ammonium which was significantly reduced with the ammonium concentration of 100 mg.L-1. The community structure of ammonium oxidizing bacteria (AOB) changed sharply with the decrease of ammonium concentraion, which was not the same as anaerobic ammonium oxidizing bacteria (ANAMMOX bacteria). Besides, the abundance of the two functional groups of bacteria reduced while the population of nitrite oxidizing bacteria (NOB) rose with the decrease of ammonium, which might be the main reason for the reduction of nitrogen removal efficiency. Consequently, some strategies are needed to reduce the loss of AOB and ANAMMOX bacteria and inhibit the growth of NOB so as to maintain the nitrogen removal performance in low ammonium concentration.

We extend the matrix expansion method to study the long time dynamics for all‐atom models of alkane chain internal dynamics. In order to focus on the influence of the poorly understood memory (often also termed ‘‘internal friction’’) contributions, the theory is compared with Brownian dynamics simulations in which the molecular solvent is replaced by a white noise source of random and frictional forces on the individual carbon and hydrogen atoms of the alkane molecule. The interaction potentials contain torsional potentials and nonbonded interactions, and the same potentials are used for both the theory and the simulations. Hence, the comparisons between theory and simulations involve no adjustable parameters. The first order theory is equivalent to a generalized Rouse model in which harmonic forces exist, in principle, between every pair of atoms in the alkane chain, with the force constants evaluated in terms of static equilibrium correlations. The first order theory provides a decent representation of the long time (t≥100 ps) portions of the C–C motion time correlation functions (dipole and orientational), but the theory is poor for the C–H correlation functions because they have correlation times much shorter than 100 ps. Various higher order mode coupling basis sets are investigated to include the long time influences of the memory terms, and the computations consider the role of the more rapid hydrogen motions in exerting a frictional drag on the slower C–C bond motions. The truncated second order basis provides a rapidly convergent and accurate representation of the long time dynamics.

We develop methods for alleviating the major impediment in the extension to larger and more complex systems of our matrix method theory for describing the long time dynamics of flexible polymers and proteins in solution. This impediment is associated with the enormous growth in size of the required basis set with the addition of higher order mode coupling basis functions, which are needed to describe the influence on the dynamics of the ‘‘internal friction,’’ or equivalently of the memory function matrices. We use the first order eigenfunctions (the generalized Rouse modes) to construct an approximate mode coupling basis. Specific applications are made to united atom models of alkanes with a white noise structureless solvent, where the theory is compared with Brownian dynamics simulations to provide a no‐parameter stringent test of the theory. Good convergence is found to the full second order treatment with the new basis set whose size scales more nearly with the size of the system rather than the cube o...

We introduce a generalized matrix expansion method for modeling the long-time dynamics of flexible molecules in solutions. Applications consider the Brownian dynamics of a united atom model alkane molecule in a white-noise structureless solvent. The time autocorrelation functions for the middle, end, and end-to-end bonds are computed for the alkane molecules from the Brownian dynamics simulations and the matrix expansion method, both using identical interaction potentials. The leading approximation of the matrix expansion method involves neglecting memory functions, but it fares very well (especially for longer chain alkanes) despite the frequent conformational transitions occurring during the Brownian dynamics trajectories. The leading approximation is deficient at short times due to the neglect of the memory terms. We describe the influence of these memory functions by appending basis functions to the generalized matrix expansion method. The added basis functions yield improved agreement between theory and the simulations, and good convergence is obtained towards the simulations for longer times. The Brownian dynamics simulations are also used to test a universal relations for the orientational correlation functions.

To study the immunophenotype and c-kit or platelet derived growth factor receptor alpha (PDGFRA) gene mutations in CD117-negative gastrointestinal stromal tumors (GISTs).Ten cases of GISTs with typical histologic features but no CD117 expression were retrieved from the archival of Department of Pathology, Peking Union Medical College Hospital, China. The cases were further evaluated for the presence of c-kit exons 9, 11, 13 and 17 mutations and PDGFRA exons 12 and 18 mutations. DNA was extracted from the paraffin-embedded tumor tissue. The PCR products were sequenced directly for the mutations. An immunohistochemical study for CD117, CD34, smooth muscle actin, desmin, S-100 protein, WT-1 and DOG-1 was also performed.Eight of the 10 cases had the mutation tests completed. C-kit mutation in exon 9 was detected in only one case. Amongst the 10 cases studied, CD34 was expressed in 9 cases. Smooth muscle actin was focally positive in 2 cases. None of them expressed desmin or S-100 protein. DOG-1 and WT-1 were diffusely positive in 5 and 4 cases, respectively. In addition, DOG1 was diffusely but weakly positive in 1 case and focally expressed in 2 cases. Three cases were focally positive for WT-1.Pathologic diagnosis of CD117-negative GISTs can be facilitated with the application of a panel of immunohistochemical markers, including DOG-1 and WT-1.

Tests are introduced of one basic approximation inherent in a recent theory for long time dynamics of flexible proteins and polymers in solution. The approximation in question concerns the neglect of memory functions, which for these systems involve a memory function matrix whose properties are not readily modeled without input from simulations. The memory function matrix affects the dynamics on all time scales, but our focus is on those portions influencing mainly the long time dynamics, which is not amenable to simulation for interesting complicated systems. Thus the tests are made on a simple, yet nontrivial system for which long time simulations are possible and provide the most stringent test of the parameter free theory. The test involves Brownian dynamics simulations of united atom models for single octane and pentadecane dynamics in a structureless solvent. The octane case, for instance, yields a 7×7 memory function matrix whose properties are more complex than those of the one‐dimensional Kramers model recently studied. More importantly, our computations determine those necessary ingredients of the memory function matrix for describing long time dynamics of flexible large molecules in solution. We compare the theoretical and simulation computations of the bond vector time autocorrelation functions. The leading approximation without memory functions fares remarkably well despite the frequent conformational transitions occurring during the Brownian dynamics trajectories. This approximation systematically leads to faster decay than the simulations due to the neglect of the long time frictional influence of the memory function matrix. We consider computations of these memory functions using both the Mori continued function formalism, and a generalization of the matrix methods introduced to treat the one‐dimensional Kramers model. A procedure is developed to obtain the long time influence of the memory function matrix. This procedure improves agreement between theory and simulation and displays good convergence towards the simulation results at the longer times (≳100 ps) for which we are interested.

To study the clinicopathologic features and diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.Nineteen cases of IPMN encountered during the period from 1999 to 2007 were studied by light microscopy and immunohistochemistry.IPMN occurred more often in males (68%). It affected patients in older age group (mean age = 59) and was located mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1 to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%), diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was performed in 18 cases. The remaining patient received bypass surgery only. Features of in-situ or invasive malignancy were present in 15 of the 19 cases (78%). Histologically, the tumor consisted of papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was noted in 12 cases and chronic pancreatitis was present in 16 cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from 1 patient who died of other disease, all were still alive. Immunohistochemical study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8 cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to 80% (mean = 38%).Malignant changes are not uncommon in IPMN. The prognosis after surgical resection however is better than that of conventional pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be related to tumor progression. The possibility of malignant transformation needs to be considered if the Ki-67 index is over 15%. Early recognition by radiologic examination (including ERCP) and pancreatic cytology would be helpful in early diagnosis. Surgical resection represents the mainstay of treatment and long-term post-operative follow up is needed.

To study the clinicopathologic features and differential diagnosis of dyshormonogenetic goiter.The clinical features, histopathologic findings and immunohistochemistry of four cases of dyshormonogenetic goiter were reviewed.Amongst the cases of dyshormonogenetic goiter studied, three were females and one male. The age of disease onset ranged from 6 to 12 years and the age at operation ranged from 13 to 28 years. Three patients presented with symptoms of hypothyroidism and one patient had normal thyroid function. On gross examination, the thyroid was multinodular and covered by fibrous capsule. Histologically, three patterns were observed. The predominant pattern was microfollicular/trabecular, with hyperplastic follicular cells associated with scanty colloid material. The second pattern was macrofollicular, the follicular cells were cuboid in shape, with inconspicuous mitotic figures. The third pattern was microcystic, with papillary component frequently seen. No normal intervening thyroid parenchyma was found. All the patients were on long-term thyroxine replacement therapy after operation and remained well.Dyshormonogenetic goiter is considered as a form of thyroid hyperplasia due to enzymatic defects in hormone synthesis. The architectural polymorphism and cellular atypia may mimic thyroid neoplasms and cause difficulties in differential diagnosis.

8-Chloro-adenosine(8-Cl-Ado) is an anti-tumor drug,which has been investigated and developed recently in China. The molecular mechanism of 8-Cl-Ado is now unclear. This study was conducted to investigate the effect of 8-Cl-Ado on the activity of transcription factor cAMP-response-element-binding protein(CREB) and its correlative mechanism in human promyelocytic leukemia cell line HL-60.MTT method was used to determine IC(50) (the concentration showing 50% of inhibition rate) of 8-Cl-Ado to HL-60. The protein levels and phosphorylated levels of CREB at different time following 8-Cl-Ado stimulation were examined using Western blot analysis. Gel shift assay was performed to examine DNA binding levels of CREB at different time following 8-Cl-Ado stimulation.(1)The IC(50) of 8-Cl-Ado to HL-60 was about 0.42 micromol/L. (2)8-Cl-Ado increased phosphorylated level of CREB rapidly, which was maximal at 30 minutes, and returned to basal level in 6 hours. The protein level of CREB was constant during 8-Cl-Ado stimulation. (3)8-Cl-Ado did not influence binding level of DNA and CREB.The increase of transcriptional activity of CREB induced by 8-Cl-Ado depends on the increased level of phosphorylated CREB, but is not associated with the protein level and DNA binging level of CREB.

A method introduced by Stillinger for finding global minima of potential surfaces and for achieving the optimization objectives of simulated annealing is shown to require caution in some of its applications. In particular, a range parameter is varied to eliminate secondary minima on the potential surface or hypersurface of the objective function of interest. We show that in some cases, using minimizations on the simplified surface to reveal minima on the more complex surface require scrutiny of the sequences of low‐energy minima, as functions of the range parameter whose variation controls the complexity of the surface.

Potential barrier heights for three different hydrogen‐atom migration pathways on C(111) are computed on the semiempirical hydrocarbon potential developed by Brenner [Phys. Rev. B 42, 9458 (1990)]. The barrier for diffusion to an adjacent absorption site is found to be 3.29 eV. Migration rate coefficients obtained from classical variational transition‐state theory indicate that such migration processes play a minor role in diamond‐film synthesis. The contribution of tunneling to the diffusion rate is shown to be negligible. The computed migration barrier to an adjacent adsorption site is in good agreement with recent results obtained by Melnik et al. using a triple‐referenced, configuration interaction method.