[Imaging risk factors for postoperative cerebral infarction in adults with ischemic Moyamoya disease].

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group (P<0.05).Preoperative TIA (OR=4.514, 95%CI: 1.920-10.611), old cerebral infarction (OR=2.856,95%CI:1.176-6.936), A1 stenosis (OR=7.027,95%CI:1.877-26.308), M1 stenosis (OR=6.968,95%CI:2.162-22.459), abnormal PCA (OR=4.114,95%CI:1.330-12.728)and unstable compensation (OR=4.488,95%CI:1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P<0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization.

Feasibility of using dynamic contrast-enhanced MRI for differentiating thymic carcinoma from thymic lymphoma based on semi-quantitative and quantitative models.

AIM: To evaluate the value of using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived parameters to differentiate thymic carcinoma and thymic lymphoma based on semi-quantitative and quantitative models. MATERIALS AND METHODS: Twenty-nine pathologically confirmed anterior mediastinum tumours in 29 patients were enrolled in this retrospective study, including 15 thymic carcinoma and 14 lymphoma patients. All the patients underwent pre-treatment mediastinum DCE-MRI. Both semi-quantitative and quantitative parameters were calculated and the volume transfer constant Ktrans, the flux rate constant between extravascular extracellular space and plasma kep, the extravascular extracellular volume fraction ve were obtained based on a modified Tofts model. DCE-MRI derived parameters were compared between thymic carcinoma and thymic lymphoma groups. RESULTS: Thymic carcinoma had significantly lower kep (p=0.040) and higher ve (p=0.018) than thymic lymphoma; however, there were no significant differences on Ktrans and semi-quantitative parameters between the two groups. ve had the highest area under the curve (cut-off value, 0.282; area under the curve, 0.748; sensitivity, 71.4%; specificity, 80%). The combination of kep and ve could increase the diagnostic performance significantly (area under the curve, 0.752; sensitivity, 57.1%; specificity, 93.3%). CONCLUSION: DCE-MRI derived parameters may have value in the differentiating thymic carcinoma and thymic lymphoma.

Differentiation of focal organising pneumonia and peripheral adenocarcinoma in solid lung lesions using thin-section CT-based radiomics.

AIM: To evaluate the predictive role of radiomics based on computed tomography (CT) in discriminating focal organising pneumonia (FOP) from peripheral lung adenocarcinoma (LA). MATERIALS AND METHODS: Institutional research board approval was obtained for this retrospective study. One hundred and seventeen patients with FOP and 109 patients with LA who underwent thin-section CT from January 2011 to August 2017 were reviewed systematically and analysed. The clinical and radiological features were established as model A and multi-feature-based radiomics as model B. The diagnostic performance of model A, model B, and model A+B were evaluated and compared via receiver operating characteristic (ROC) curve analysis and logistic regression analysis. RESULTS: Sex, symptoms, necrosis, and the halo sign were identified as independent predictors of LA. The area under the ROC curve (Az value), accuracy, sensitivity, and specificity of model A were 0.839, 75.7%, 82.6%, and 69.2% respectively. Model B showed significantly higher accuracy than model A (83.6% versus 75.7%, p=0.032). The top four best-performing features, WavEnLH_s-3, WavEnHH_s-3, Teta3, and Volume, performed as independent factors for discriminating LA. Regression analysis indicated that model B had superior model fit than model A with Akaike information criterion (AIC) values of 73.6% versus 59.1%, respectively. Combining model A with model B is useful in achieving better diagnostic performance in discriminating FOP from LA: the Az value, accuracy, sensitivity, and specificity were 0.956, 87.6%, 85.3%, and 89.7% respectively. CONCLUSIONS: Radiomics based on CT exhibited better diagnostic accuracy and model fit than clinical and radiological features in discriminating FOP from LA. Combination of both achieved better diagnostic performance.

Using the CT features to differentiate invasive pulmonary adenocarcinoma from pre-invasive lesion appearing as pure or mixed ground-glass nodules.

OBJECTIVE: To differentiate pre-invasive lesion from invasive pulmonary adenocarcinoma (IPA) appearing as ground-glass nodules (GGNs) using CT features. METHODS: 149 GGNs were enrolled in this study, with 74 pure GGNs (p-GGNs) and 75 mixed GGNs (m-GGNs). Firstly, univariate analysis was used to analyse the difference of CT features between pre-invasive lesion and IPA. Then, multivariate analysis was conducted to identify variables that could independently differentiate pre-invasive lesion from IPA. Receiver operating characteristic curve analysis was performed to evaluate the differentiating value of identified variables. RESULTS: In the p-GGNs, multivariate analysis showed that the amount of blood vessels was an independent risk factor. Using the amount of blood vessels "≥1" as the diagnostic criterion, we could diagnose IPA with a sensitivity of 100%. Using the amount of blood vessels "=0" as the diagnostic criterion, we could diagnose pre-invasive lesions with a specificity of 100%. In the m-GGNs, multivariate analysis showed that the volume of solid portion (VSolid) and pleural indentation were two independent risk factors. One further model was constructed using these two variables: model = 2.508 × (VSolid + 1.407) × (pleural indentation - 1.016). Using the new model, improved diagnostic ability was achieved compared with using VSolid or pleural indentation alone. CONCLUSION: The amount of blood vessels through the p-GGNs would be an important criterion during clinical management, while VSolid and pleural indentation seemed important for m-GGNs. Moreover, the new model could further improve the differentiating value for m-GGNs. ADVANCES IN KNOWLEDGE: CT features are useful in differentiating pre-invasive lesion from IPA appearing as GGNs.

Development of an indirect ELISA with epitope on nonstructural protein of Muscovy duck parvovirus for differentiating between infected and vaccinated Muscovy ducks.

UNLABELLED: The aim of this study was to develop an indirect enzyme-linked immunosorbent assay (i-ELISA) based on epitope AA503-509 (RANEPKE), which is on nonstructural protein of Muscovy duck parvovirus (MDPV). Sera (100) from negative and vaccinated Muscovy ducks were compared with infected sera (240) to establish the cut-off value of this i-ELISA. There was a significant difference between the positive and negative populations (P < 0·05). The adoption of this positive-negative threshold value for this i-ELISA assay resulted in specificity of 98·0%. This i-ELISA could be used as a diagnostic tool for differentiating infected Muscovy ducks from Muscovy ducks vaccinated with inactivated virus. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we developed an i-ELISA based on epitope AA503-509 (RANEPKE), which is on nonstructural protein of MDPV. This i-ELISA could be used as a diagnostic tool for differentiating infected Muscovy ducks from Muscovy ducks vaccinated with inactivated virus.

CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma.

Generation of a T cell-mediated antitumor response depends on T cell receptor engagement by major histocompatibility complex/antigen as well as CD28 ligation by B7. CTLA-4 is a second B7 receptor expressed by T cells upon activation that, unlike CD28, appears to deliver an inhibitory signal to T cells. Recently, we and others demonstrated that administration of an anti-CTLA-4 antibody was sufficient to promote regression of several murine tumors. However, certain tumors, such as the SM1 mammary carcinoma, remain refractory to this type of immunotherapy. In the present study, we report that the combination of both CTLA-4 blockade and a vaccine consisting of granulocyte-macrophage colony-stimulating factor-expressing SM1 cells resulted in regression of parental SM1 tumors, despite the ineffectiveness of either treatment alone. This synergistic therapy resulted in long-lasting immunity to SM1 and depended on both CD4(+) and CD8(+) T cells. Interestingly, synergy was not observed between CTLA-4 and a B7-expressing SM1 vaccine. Given that granulocyte-macrophage colony-stimulating factor promotes differentiation and activation of dendritic cells as well as enhances cross-priming of T cells to tumor-derived antigens and that SM1 is major histocompatibility complex class II-negative, our findings suggest that CTLA-4 blockade acts at the level of a host-derived antigen-presenting cell. In addition, these results also support the idea that the most effective and synergistic vaccine strategy targets treatments that enhance T cell priming at the level of host-derived antigen-presenting cells.

Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma.

In recent years, tumor immunotherapy has begun to exploit the emerging knowledge of the mechanisms of T cell activation to enhance the immune responses to tumors. However, many tumors, despite genetic modification to express co-stimulatory molecules or cytokines, are not readily rejected due to their inherently poor immunogenicity. In the present study, we tested whether expression of the co-stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM-CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1. However, co-expression of B7 and IFN-gamma was sufficient to result in regression of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma-expressing SM1 tumor resulted in protection from rechallenge not only with the unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support the idea that although B7 expression alone may not be sufficient for rejection of certain tumors, the immune system may be stimulated to mount an effective anti-tumor immune response by the co-expression of both the co-stimulatory ligand and a cytokine.

Purification and characterization of lupus anticoagulant like protein from Agkistrodon halys brevicaudus venom.

By means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)(Q/K). It was devoid of phospholipase A, fibrino(geno)lytic, 5'-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell's viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.

Purification and characterization of L-amino acid oxidase from king cobra (Ophiophagus hannah) venom and its effects on human platelet aggregation.

Venoms of several snake species contain large amounts of L-amino acid oxidase but its effects on human plasma coagulation and platelet aggregation have not been explored. We have purified L-amino acid oxidase from king cobra venom through CM-Sephadex C-25, Sephadex G-100 and DEAE Sephadex A-50 chromatographies. The purified enzyme has a mol. wt of 135,000 as determined by gel filtration and 65,000 by SDS-PAGE under non-reducing and reducing conditions. Incubation of plasma with L-amino acid oxidase at 200 micrograms/ml did not affect prothrombin time, activated partial thromboplastin time, or thrombin time. Upon addition of L-amino acid oxidase, platelets in platelet-rich plasma were aggregated. The enzyme-induced aggregation was abolished by catalase. The aggregation was also inhibited by indomethacin, aspirin, ethylenediaminetetraacetate, sodium nitroprusside, prostaglandin E1, mepacrine and verapamil, but not by heparin, hirudin, creatine phosphate/creatine phosphokinase or antimycin/2-deoxy-D-glucose. These results suggest that L-amino acid oxidase induces human platelet aggregation through the formation of H2O2, and subsequent thromboxane A2 synthesis requiring Ca2+ but independent of ADP release. The platelet aggregation caused by L-amino acid oxidase is likely to contribute to toxicity inflicted by cobra venom.

[Effect of total alkaloids of kudouzi (Sophora alopecuroides L.) on tolerance to anoxia in mice].

To several anoxia mice models, total alkaloids of Kudouzi (TASa) can prolong their tolerance time (ip < 1/10, 1/5LD50/kg, P < 0.05-0.01). In the experiment of myocardial ischemia induced by pituitrin, TASa decreased significantly the ST change in ECG (P < 0.05). The acute LD50 of TASa by ip was found to be 130.66 +/- 22.64 mg/kg for mice.

Lipid studies in primary gout.

Serum total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride were measured in three groups of male patients with primary gout. The groups were defined by the presence of 0, 1, or more than 1 coexisting medical conditions or cardiac risk factors (coronary heart disease, hypertension, diabetes, proteinuria, overweight). Mean values of total, LDL, and HDL cholesterol were lower in patients with one or more associated conditions than in those with none. By contrast, triglyceride levels were significantly higher and exceeded the desirable range. Distributions of individual values of all lipid parameters except triglycerides were similar along the three groups. Triglyceride values, however, were significantly higher in patients with multiple complications. Observed differences in lipid values could not be correlated with patient age or type of nature of medication received. High triglycerides and LDL cholesterol are not a feature of uncomplicated gout in men. HDL cholesterol tends to be normal and triglyceride mildly elevated. Only in patients with two or three associated medical conditions are high triglycerides or low HDL cholesterol common. Our results suggest that these findings are independently related to concurrent disease and that gout is not necessarily in itself a risk factor for cardiovascular or diabetic disease.

Impact of associated medical conditions on clinical features of gout.

In view of the various available drugs, we are now in a very much better situation for treatment of gout, with and without associated medical conditions. When several drugs are employed in one single patient, however, one may run into drug interactions, resulting into exaggerated hyperuricemia or induced acute gouty arthritis. In lieu of the various associated medical conditions, controlled or uncontrolled, the clinical features of gout may be modified. Accordingly, one must treat the patient's gout as well as his various stages of the associated medical conditions, and each patient must be individualized.

Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis.

Four patients with recurrent cystine stones and 5 with rheumatoid arthritis (RA) were studied. After a single dose of D-penicillamine to cystinuric patients, cystine excretion decreased considerably. Cysteine-penicillamine mixed disulfide (CSSP) and penicillamine disulfide (PSSP) metabolites appeared within 1-2 h (CSSP/PSSP approximately equal to 4.8-8.6). In RA, cystine excretion remained negligible (CSSP/PSSP approximately equal to 1.4-2.9). With daily D-penicillamine in RA (CSSP/PSSP ratios were usually greater than 7 in those with favorable clinical response. CSSP/PSSP ratios may help to predict prognosis and adjust penicillamine dosage. Coadministration of probenecid is contraindicated in hyperuricemic cystinuric patients because of increased cystine and decreased CSSP and PSSP excretion.

Incorporation of 15N from glycine into uric acid in gout: a follow-up study.

Over-incorporation of 15N-labeled glycine into uric acid indicates over-production of uric acid by de novo purine biosynthesis. This metabolic aberration, though considered to be inborn (3), may be modified by changing of life style, aging and long-term therapy. In the patient under study, the protracted use of allopurinol seems to have played the most important role. Aging contributed to a certain extent, and changing life style was the least significant factor.

Impaired renal function gout: its association with hypertensive vascular disease and intrinsic renal disease.

Inulin clearance was measured in 624 patients with gout, and para-aminohippuric acid (PAH) clearance in 359; Group I consisted of 397 patients with uncomplicated gout; Group II, 191 patients with hypertension and/or ischemic heart disease; and Group III, 36 patients with chronic renal disease. Mean inulin clearance was normal in Group I, slightly depressed in Group II and more markedly decreased in Group III. There was some reduction in PAH clearance in all groups, but not in the very young patients with no complications. A disproportionate reduction in PAH clearance was noted in Groups II and III, particularly in the older patients with longer duration of gout. Uncomplicated gout, except in rare cases of fulminating gout, does not lead to decreased renal hemodynamics. An increased incidence of tophi correlates with decreased renal function, but incidence of renal calculi does not. Renal insufficiency when seen in patients with gout usually correlates with coexistence of hypertension, ischemic heart disease, or primary preexistent renal insufficiency.

Long-term follow-up of incorporation of 15N from glycine into uric acid in gout.

The incorporation of 15N-glycine into urinary uric acid was studied in three gouty patients, repeating a study carried out 13 to 27 years ago. The 15N incorporation attained a lower maximum and declined less rapidly in the repeat study in all three patients. The cumulative 15N incorporation into uric acid was reduced to one half of that determined previously. Similarly, urinary uric acid excretion was less, along with a lower uric acid nitrogen to total nitrogen ratio. The data indicate changes in the nature of the metabolic aberrations, which are apparently related to long-term drug therapy, changes in lifestyle, aging and associated medical complications.

Pharmacokinetic and clinical studies of carprofen in gout.

Carprofen, a carbazole derivative, has been found to be highly potent as anti-inflammatory agent. After a single dose of 100 mg, plasma caprofen peaked in 1 to 2 hours, and t 1/2 was estimated to be 4.4 +/- 1.4 hours, based on a monoexponential fit of the data. Cumulative urinary excretion of total carprofen in 24 hours was almost 30% of the dose, chiefly as glucuronide conjugate. With simultaneous administration of carprofen and probenecid, peak plasma carprofen doubled. The t 1/2 was somewhat prolonged, and urinary excretion was significantly reduced. The t 1/2 of probenecid was not changed, and probenecid uricosuria was unaffected. Carprofen was found to be quite effective for acute gouty arthritis. The drug was well tolerated. Some mild diarrhea developed in one of the 14 patients. No other side effects were observed. The efficacy of carprofen for acute gouty arthritis deserves further trial.