Disrupted topological organization of the default mode network in mild cognitive impairment with subsyndromal depression: A graph theoretical analysis.

AIMS: Subsyndromal depression (SSD) is common in mild cognitive impairment (MCI). However, the neural mechanisms underlying MCI with SSD (MCID) are unclear. The default mode network (DMN) is associated with cognitive processes and depressive symptoms. Therefore, we aimed to explore the topological organization of the DMN in patients with MCID. METHODS: Forty-two MCID patients, 34 MCI patients without SSD (MCIND), and 36 matched healthy controls (HCs) were enrolled. The resting-state functional connectivity of the DMN of the participants was analyzed using a graph theoretical approach. Correlation analyses of network topological metrics, depressive symptoms, and cognitive function were conducted. Moreover, support vector machine (SVM) models were constructed based on topological metrics to distinguish MCID from MCIND. Finally, we used 10 repeats of 5-fold cross-validation for performance verification. RESULTS: We found that the global efficiency and nodal efficiency of the left anterior medial prefrontal cortex (aMPFC) of the MCID group were significantly lower than the MCIND group. Moreover, small-worldness and global efficiency were negatively correlated with depressive symptoms in MCID, and the nodal efficiency of the left lateral temporal cortex and left aMPFC was positively correlated with cognitive function in MCID. In cross-validation, the SVM model had an accuracy of 0.83 [95% CI 0.79-0.87], a sensitivity of 0.88 [95% CI 0.86-0.90], a specificity of 0.75 [95% CI 0.72-0.78] and an area under the curve of 0.88 [95% CI 0.85-0.91]. CONCLUSIONS: The coexistence of MCI and SSD was associated with the greatest disrupted topological organization of the DMN. The network topological metrics could identify MCID and serve as biomarkers of different clinical phenotypic presentations of MCI.

The liver microenvironment orchestrates FGL1-mediated immune escape and progression of metastatic colorectal cancer.

Colorectal cancer (CRC) patients with liver metastases usually obtain less benefit from immunotherapy, and the underlying mechanisms remain understudied. Here, we identify that fibrinogen-like protein 1 (FGL1), secreted from cancer cells and hepatocytes, facilitates the progression of CRC in an intraportal injection model by reducing the infiltration of T cells. Mechanistically, tumor-associated macrophages (TAMs) activate NF-ĸB by secreting TNFα/IL-1ß in the liver microenvironment and transcriptionally upregulate OTU deubiquitinase 1 (OTUD1) expression, which enhances FGL1 stability via deubiquitination. Disrupting the TAM-OTUD1-FGL1 axis inhibits metastatic tumor progression and synergizes with immune checkpoint blockade (ICB) therapy. Clinically, high plasma FGL1 levels predict poor outcomes and reduced ICB therapy benefits. Benzethonium chloride, an FDA-approved antiseptics, curbs FGL1 secretion, thereby inhibiting liver metastatic tumor growth. Overall, this study uncovers the critical roles and posttranslational regulatory mechanism of FGL1 in promoting metastatic tumor progression, highlighting the TAM-OTUD1-FGL1 axis as a potential target for cancer immunotherapy.

SOCS3 protein expression predicts the responses of advanced non-small cell lung cancer patients to platinum-based chemotherapy.

Background: This study sought to assess the relationship between suppressor of cytokine signaling 3 (SOCS3) expression, SOCS3 promoter methylation status, and platinum-based chemotherapy responses in advanced non-small cell lung cancer (NSCLC) patients. Methods: A total of 400 advanced NSCLC patients with inoperable disease were enrolled in this study. All the patients underwent platinum-based chemotherapy treatment, and the clinical and prognostic outcomes of these patients were analyzed. The SOCS3 protein expression and SOCS3 promoter methylation status of the tumor tissues in these patients were also tested by immunohistochemistry and polymerase chain reaction (PCR), respectively. In addition, we knocked down SOCS3 expression via small-interfering RNA (siRNA) in the lung cancer cell lines and conducted in vitro analyses to examine cell viability and apoptosis. Results: Patients with higher expression levels of SOCS3 were found to have a lower average tumor stage, higher average tumor differentiation, and higher rates of positive chemotherapy responses than those with lower expression levels of SOCS3. SOCS3 promoter methylation was also found to be correlated with chemotherapy responses in these patients. In the prognostic analyses, only SOCS3 expression, but not SOCS3 promoter methylation, was found to be predictive of outcomes in advanced NSCLC patients. We also found that the pro-apoptotic effects of SOCS3 were mediated by the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways in the lung cancer cells. Conclusions: Currently, there is a lack of reliable biomarkers for predicting the responses of NSCLC patients to chemotherapy. Our results may aid in clinical evaluations of NSCLC patients.

The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid-Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer.

SIGNIFICANCE: Secretion of TNFα by tumor-associated macrophages stimulates cancer cells to upregulate lncRNA MALR, which induces ILF3 liquid-liquid phase separation and activation of HIF1α signaling to promote cancer progression.

Splenic Kaposi's sarcoma in a human immunodeficiency virus-negative patient: A case report.

BACKGROUND: Kaposi's sarcoma (KS) is a malignancy that usually affects the skin of the lower extremities, and may involve internal organs. It originates from the vascular endothelium. It is well known that the development of KS is associated with human herpes virus 8 (i.e. HHV8) infections. Sporadic KS cases have mainly been found in Africa. Isolated splenic KS in Asia has rarely been reported. We present here a case of KS primarily involving the spleen in a human immunodeficiency virus (HIV)-negative Chinese patient. CASE SUMMARY: A 50-year-old male patient was admitted to hospital due to abdominal distension and discomfort, reduced food intake and weight loss. Medical examination revealed that the patient had moderate anemia, a low platelet count, slight fatty liver and a huge mass in the spleen. Spleen lymphoma was considered. An anti-HIV test was negative. The whole spleen was surgically excised. The final pathological diagnosis was nodular stage spleen KS, and the patient underwent total splenectomy. He recovered well and was discharged from hospital 12 d after surgery. Two weeks later, the patient developed liver metastasis and died within 1 mo after surgery. CONCLUSION: KS is difficult to diagnose and pathological examination is necessary. KS has a poor prognosis and should be diagnosed and treated early to improve survival.

The remediation effects of working memory training in schizophrenia patients with prominent negative symptoms.

Introduction: Negative symptoms, particularly amotivation and anhedonia, are important predictors of poor functional outcome in patients with schizophrenia. There has been interest in the efficacy and mechanism of non-pharmacological interventions to alleviate these symptoms. The present study aimed to examine the remediation effect of working memory (WM) training in patients with schizophrenia with prominent negative symptoms.Methods: Thirty-one schizophrenia patients with prominent negative symptoms were recruited and assigned to either a WM training group or a treatment-as-usual (TAU) control group. The WM training group underwent 20 sessions of training using the dual n-back task over one month. A functional neuroimaging paradigm of the Affective Incentive Delay (AID) task was administered before and after the training intervention to evaluate the remediation effect of the intervention.Results: Our results showed that the WM training group demonstrated significant improvement in the WM training task and inattention symptoms. Compared with the TAU group, increased brain activations were observed at the right insula and the right frontal sub-gyral after WM training in the training group.Conclusions: These findings support the efficacy of WM training in ameliorating hedonic dysfunction in schizophrenia patients with prominent negative symptoms.

Clinical utility of the dual n-back task in schizophrenia: A functional imaging approach.

The neural correlate of working memory (WM) impairment in schizophrenia is key to the understanding of the cognitive deficits observed in this disorder. We sought to determine the clinical validity of the dual version n-back paradigm in patients with schizophrenia, and whether schizophrenia patients exhibit altered brain activation patterns compared with healthy controls in this dual version WM measure using functional magnetic resonance imaging. Patients with schizophrenia (n = 20) and healthy controls (n = 24) performed the dual n-back task that consists of both visuospatial and auditory-verbal n-back streams, in which participants were required to monitor and update the contents from these two different inputs simultaneously. Significant positive correlations were found between performance in the dual 2-back condition and another measure of WM capacity and IQ estimates. Moreover, hypoactivation was observed at the right middle frontal gyrus and the posterior parietal regions in schizophrenia participants compared with healthy controls. The right hippocampus was less deactivated in schizophrenia patients compared with healthy controls. Our results support the clinical utility of the dual n-back task in schizophrenia and may have implications for the development of specific cognitive training targeting these impaired neural substrates in relation to WM in patients with schizophrenia.

NF-κB1 promoter-94ins/delATTG polymorphisms correlate with the acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: To clarify the correlation between the NF-κB1 gene initiation sequence -94ins/delATTG polymorphisms and the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: Blood samples of 260 AECOPD patients were collected from September 2013 to September 2015 in the department of respiratory medicine, the Third Affiliated Hospital of Southern Medical University. Blood samples of 260 healthy subjects were collected as a control group. DNA was extracted using genomic DNA extraction kits and analyzed on a DNA quantitative analyzer. Data analysis was performed using Rotor-Gene (60001.7) to determine genotypes. SPSS20.0 was used to compare -94ins/delATTG polymorphisms between patients and healthy subjects. The relationship between the promoter sequence -94ins/delATTG of NF-κB1 genotypes and AECOPD were further analyzed. RESULTS: We detected ins/ins, insertion or deletion (ins/del) and del/del genotypes from both the AECOPD and healthy control groups. The distribution of the three genotypes were consistent with the Hardy-Weinberg equilibrium law. The composition ratios of ins/ins, ins/del, del/del genotype distributions differed between AECOPD and control groups (P<0.05). The differences in ins/ins, ins/del and del/del genotype distributions between the two groups also significantly differed (P<0.05). The distribution of allele frequencies was comparable between the groups (P>0.05). The distribution ratio showed no relevance to the smoking index and clinical phenotypes of AECOPD patients, whether carrying ins/ins + ins/del genotypes or del/del genes (P>0.05). Compared to AECOPD patients with del/del genotypes, AECOPD patients with ins/ins + ins/del genotypes had a lower body mass index (BMI), a higher COPD assessment test (CAT) score, a larger number of acute episodes and longer hospital stays (P<0.05). CONCLUSIONS: The detection of the -94ins/delATTG polymorphism in patients with AECOPD can predict disease prognosis. The BMI of patients with AECOPD was significantly lower in patients carrying the -94insATTG gene. Gene detection is therefore important in patients carrying ins/ins or ins/del genotypes following admission.

GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer's Disease.

Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-ß protein precursor (AßPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature. Subchronic treatment of adult AßPP/PS1 mice with GDF11 rescued cognitive function and ameliorated cerebrovascular function. In particular, the de novo genesis of small blood vessels and the expression of vascular-related proteins were significantly higher than in the vehicle-treated AßPP/PS1 mice, whereas the expressions of the inflammatory markers Iba-1 and GFAP significantly decreased in proportion to the lower ratio of two forms of amyloid-ß (Aß40/42). Daily intravenous treatment with GDF11-injection can rejuvenate respects of cognition and cerebrovascular changes in AD mice.

Striatal dysfunction in patients with schizophrenia and their unaffected first-degree relatives.

Despite empirical findings showing that patients with schizophrenia and their unaffected first-degree relatives have deficits in processing monetary incentives, it is unclear whether similar deficits could be demonstrated for affective incentives. Twenty-six patients with schizophrenia and 26 age and gender matched healthy controls; 23 unaffected first-degree relatives and 23 matched healthy controls were recruited to complete a Monetary Incentive Delay (MID) task and an Affective Incentive Delay (AID) task in a 3-Tesla MRI scanner. Hypoactivation in the dorsal striatum when anticipating monetary incentives were found in patients with schizophrenia and their unaffected first-degree relatives compared with healthy controls. Furthermore, patients with schizophrenia showed hyperactivation in the ventral striatum when receiving both monetary and affective incentives. These findings suggest that disorganized striatal function, regardless of incentive types, may be present in patients with schizophrenia and before the onset of illness in their first-degree unaffected relatives.

Catalpol regulates cholinergic nerve system function through effect on choline acetyl-transferase not M receptor affinity.

OBJECTIVE: To explore the effect of catalpol on choline acetyl-transferase and M receptor affinity in a PC12 cell model and a rat model induced by beta-amyloid 25-35 (Aß25-35). METHODS: In PC12 cells, catalpol (10µmol/l, 100µmol/) or saline was retained in the medium and Aß25-35 (final concentration 20µmol/l) was added. Choline acetyl-transferase (ChAT) expression was determined by immunocytochemistry, ChAT activity measured by radioenzymatic assay, and M receptor (muscarinic receptor) affinity determined by (3)H-QNB binding test. In Wistar rats, Aß25-35 was injected intracerebroventricularly to establish AD model. After injection of Aß25-35, the rats were injected catalpol at 5 and 10mg/kgd(-1) intraperitoneally for the next 7 days, and saline for the control rats. ChAT expression, ChAT activity and M receptor affinity were tested. Cells and rats all were divided into four groups: Group A (control), Group B (model), Group C (catalpol low dose), and Group D (catalpol high dose). RESULTS: Compared with control, both PC12 cell and rat AD models showed decreased expression and activity of ChAT (p<0.01), but M receptor affinity remained the same (p>0.05). Compared with model group, treatment of catalpol increased expression and activity of ChAT of PC12 cell and rat AD model induced by Aß25-35, p<0.05 or p<0.01 respectively. But there was no difference of M receptor affinity among the four groups (p>0.05). M receptor affinity remained the same as concentration of catalpol increased gradually in atropine competition experiments (p>0.05). CONCLUSIONS: Catalpol could regulate the cholinergic nerve system function from its effect on ChAT and may have beneficial effect for treatment of AD, but had no effect on M receptor affinity.

Catalpol regulates function of hypothalamic-pituitary-adrenocortical-axis in an Alzheimer's disease rat model.

AIMS: To investigate the regulating effects of catalpol on the hypothalamic-pituitary- adrenocortical-axis (HPA) in an Alzheimer's disease (AD) rat model. METHODS: Healthy male Wistar Rats were selected. The AD model was generated by orthotopic injection of beta-amyloid 25-35 (Abeta25-35) into the right lateral ventricle. The animals were divided into five study groups: Catalpol at low dose (5 mg/kg), Catalpol at high dose (10 mg/kg), model control group and sham surgery control group, n = 9 respectively. The serum concentration of hydrocortisone (HYD), adrenocorticotropin (ACTH) and corticotropin releasing hormone (CRH) determined by Enzyme-Linked Immunosorbent Assay (ELISA). Structural alterations of the hypothalamus were examined by H&E stain and electron microscope. The CRH receptor 1 (CRHR1) positive neurons were detected with immunohistochemistry. RESULTS: Serum HYD level was significantly increased (p < 0.01), and both ACTH and CRH were dramatically decreased (p < 0.01) in the AD model group rats compared with normal control rats at day 7. Catalpol treatment was able to improve the hormone secretion disorder in AD model group rats compared with the model group (p < 0.01 or p < 0.05) in particular at 21 days. Structure damage of hypothalamus in the AD rat as evidenced less CRHR1 positive neurons, rough endoplasmic reticulum dilation and degranulation, and mitochondrial swelling under electron microscope. Catalpol treatment at both high and low doses was able to alleviate the structure damage of the hypothalamus in the AD rats. CONCLUSIONS: Catalpol could improve the endocrine function of the HPA and alleviate the structural damage of hypothalamus in AD rats.

Experimental quasi-single-photon transmission from satellite to earth.

Free-space quantum communication with satellites opens a promising avenue for global secure quantum network and large-scale test of quantum foundations. Recently, numerous experimental efforts have been carried out towards this ambitious goal. However, one essential step--transmitting single photons from the satellite to the ground with high signal-to-noise ratio (SNR) at realistic environments--remains experimental challenging. Here, we report a direct experimental demonstration of the satellite-ground transmission of a quasi-single-photon source. In the experiment, single photons (~0.85 photon per pulse) are generated by reflecting weak laser pulses back to earth with a cube-corner retro-reflector on the satellite CHAMP, collected by a 600-mm diameter telescope at the ground station, and finally detected by single-photon counting modules after 400-km free-space link transmission. With the help of high accuracy time synchronization, narrow receiver field-of-view and high-repetition-rate pulses (76 MHz), a SNR of better than 16:1 is obtained, which is sufficient for a secure quantum key distribution. Our experimental results represent an important step towards satellite-ground quantum communication.

[Effects of DAPT on biological activity of hematopoietic stem cells in mice].

This study was to investigate the effects of DAPT (N-[N-(3,5-difluorophenacetyl-L:-alanyl)]-S-phenylglycine-butyl ester) on cell cycle, apoptosis, differentiation and expansion of hematopoietic stem cells (HSC) of mouse and to elucidate the possible mechanisms. The mRNA expressions of cell cycle-related genes p18, p21, p27, CDK1, CDK2, CDK4, CDK6, and apoptosis-related genes Bcl-2, Bcl-xl, mcl-1, Bax, Bim, p53, Puma were measured by real-time PCR. The cell cycle and apoptosis of Lin(-)c-kit(+)Sca-1(+) marked cells and CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow cells were detected by flow cytometry. The differentiation level of HSC was determined by single cell culture. The expansion of HSC were measured with long-term culture. The results indicated that the mRNA expression of the cell cycle related-genes CDK1, CDK2, CDK4, CDK6, p27 in Lin(-) c-kit(+)Sca-1(+) marked cells increased (P < 0.05), the expression of p18, p21 decreased (P < 0.05), the expression of the apoptosis related-genes Bcl-2, Bcl-xl, Bax, p53, Puma in Lin(-) c-kit(+)Sca-1(+) marked cells increased (P < 0.05), the expression of Bim decreased (P < 0.05), the expression of Mcl-1 had not changed (P > 0.05) after treatment with DAPT 1 µmol/L for 5 d. The changes of cell cycle of Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow had no statistical significance after treatment with DAPT 1 µmol/L for 5 d, CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow at G(0) phase decreased and at G(1) phase increased after treatment with DAPT 1 µmol/L for 5 d (P < 0.05); the apoptotic fractions of Lin(-) c-kit(+) Sca-1(+) marked cells and CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow increased after treatment with DAPT 1 µmol/L for 5 d (P < 0.05). The changes of colony number, average number of cells in wells and their differentiation had no statistical significance (P > 0.05) after treatment with DAPT 1 µmol/L for 10 d. Expansion of HSC in bone marrow of mouse decreased after treatment with DAPT 1 µmol/L for 3 d. It is concluded that DAPT not only enhances the exhaustion of CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow cells of mouse, but also enhances the apoptosis of Lin(-)c-kit(+)Sca-1(+) marked cells and CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in bone marrow cells of mouse. DAPT also reduces the expansion of HSC. However, the changes of survival and differentiation of single CD34(-)Lin(-)c-kit(+)Sca-1(+) marked cells in mouse bone marrow cells have no statistical significance.

[Differential expression of oxidative reductases in different subsets of mouse hematopoietic cells].

Hematopoietic stem cells (HSC) are the source of all blood cells, which can differentiate into various hematopoietic hierarchy cells. Physiological level of reactive oxygen species (ROS) plays an important role in regulating functions of HSC as excessive ROS is harmful to HSC. Oxidative reductases and antioxidants can eliminate cellular ROS to maintain ROS homeostasis and thus avoid excessive ROS-caused damages. There are several types of oxidative reductases in cells such as catalase, manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1), thioredoxin reductase 1 (Txrnd1) and Nqo1 [NAD(P)H dehydrogenase quinone 1]. However, the functional roles of various oxidative reductases in regulating ROS level in hematopoietic cells remain unclear. This study was to investigate the expression patterns of these oxidative reductases in mouse hematopoietic cells that were sorted out via flow cytometry and to find out important oxidative reductases involving in HSC ROS regulation. The expression of various oxidative reductases was detected by semi-quantitative real-time PCR. The results showed that the expression level of catalase in T cell population was 0.14 times that in LT-HSC population (P < 0.05). The expression levels of MnSOD in CLP population and myeloid cells were 0.56 and 0.47 times that in LT-HSC population respectively (P < 0.05). The expression levels of GPX1 in ST-HSC, GMP, Myeloid cells, MEP, T lymphocytes and B lymphocytes were 1.79, 2.96, 2.07, 0.58, 0.10, 0.6 times that in LT-HSC population respectively (P < 0.05). The expression levels of Txrnd1 in ST-HSC, MPP, CMP, GMP, Myeloid cells, T lymphocytes and B lymphocytes were 3.36, 3.18, 4.19, 6.39, 4.27, 0.016, 0.56 time that in LT-HSC population, respectively (P < 0.05). The expression levels of Nqo1 in ST-HSC, MPP, CMP, GMP, CLP and B cell were 0.30, 0.17, 0.25, 0.10, 0.04, 0.01 times that in LT-HSC population, respectively (P < 0.05). It is concluded that the expression levels of oxidative reductases (catalase, MnSOD, GPX1, Txrnd1 and Nqo1) in hematopoietic hierarchy cells are cell-type specific. It suggests that reductases may play divergent roles in various hematopoietic cell populations. More importantly, the expression level of Nqo1 in LT-HSC population significantly increased as compared with other cell populations, thereby suggesting its unique regulatory role in HSC.

[Investigation of articular cartilage using FTIR microspectroscopy for guinea pig with spontaneous osteoarthritis].

In-situ analysis the chemical composition of tibial articular cartilage of female Hartley guinea pigs with Fourier transform infrared (FTIR) microspectroscopy was conducted. The infrared spectrum survey consists of three ages (1 months, 2 months and 3 months) and three cartilage layers (surface, middle and deep). The results demonstrated that with ages increasing, the peak positions of main absorbance bands in surface and middle shifted to a lower wavenumber, and in deep they shifted to a lower wavenumber first, then shifted to a higher wavenumber. Infrared spectrum character of collagen, nucleic acid and proteoglycan were compared and analyzed. The ratios of I1 657/I 1 548, I1 074/I1 548 and I1 074/I1 237 tend to decrease with ages increasing in surface and middle. However, the ratios at 2 months are less than other ages in deep. These results are consistent with the regular pattern of cartilage ingredient change in different degradation stage, while the tibial platform images created by microscopic spectral imaging technology is highly compliant with pathology description. The authors' primary result illustrated that FTIR microspectroscopy can be used for in-situ analysis of molecular constituents of different levels cartilages. The molecular information obtained from the study is important for understanding the pathogenesis of cartilage diseases.

[Observation of CT three-dimensional reconstruction in the treatment of standard manipulation for lumbar intervertebral disc herniation].

OBJECTIVE: To observe the morphological change of prominence through CT three-dimensional reconstruction before and after manipulative treatment and in order to investigate biomechanical effect of manipulation in treating lumbar intervertebral disc herniation (LIDH). METHODS: From December 2009 to May 2010, 24 patients with LIDH (32 herniated discs) with the unilateral typing,which were treated with manipulation (on alternate day one time and every time about 20 min, 3 weeks as a course of treatment). There were 10 males and 14 females, ranging in age from 25 to 54 years with an average of 36.2 years, in course of disease from 2 days to 10 years with an average of 6.9 years. Protrusible 12 discs were in L4,5 and 20 discs were in L5S1. According to typing of distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 5 cases were type I, 13 cases were type II and 6 cases were type III. After a course of treatment,the morphological changes of prominences were analyzed in the same level of CT three-dimensional reconstruction, including contour map of nerve root sheath side distance (TD), the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), the deviated angle of prominence (AN value) and the sagittal index (SI value). RESULTS: From the contour map of TD, 19 patients (79.2% of the total) can be identified morphological changes after the treatment; from the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 7 cases with type II turned into type I and 2 cases with type III turned into type II after treatment; AN value increased after treatment (P<0.05),it showed prominence occurred morphological change toward deviated direction of intervertebral foramina; there was no significant difference in SI value between before and after treatment (P>0.05). CONCLUSION: Standard manipulation can make prominence change, the prominence and nerve roots release, and mutual position improve,which can provide imaging evidence for the study in biomechanical effects.

Computed tomographic cholangiography in living liver transplant donors: factors determining the degree of contrast enhancement.

OBJECTIVE: To determine factors affecting liver and bile duct contrast enhancement during computed tomographic cholangiography (CTC) in living-donor transplant candidates. METHODS: Forty-four candidates underwent preoperative triphasic CT followed by intravenous infusion of 20 mL of iodipamide for CTC. Body size indices and liver volume were correlated to parenchymal and biliary enhancement. Bile duct visibility was compared to duct enhancement. RESULTS: Poorly visualized first- and second-order bile ducts demonstrated diminished enhancement (P < 0.015). Both CTC parenchymal and biliary enhancement correlated inversely with body surface area, height, and weight (P < 0.001); inverse correlation was also seen between liver volume and parenchymal enhancement (P < 0.001). A moderately positive correlation was noted between CTC biliary and parenchymal portal venous enhancement (r = 0.421; P = 0.004). CONCLUSIONS: Computed tomographic cholangiography parenchymal and biliary enhancement diminishes with increased body size and liver volume, supporting a need for adjustable contrast dosing. Portal venous parenchymal enhancement may serve as a preinfusion indicator.

Azaxanthene based selective glucocorticoid receptor modulators: design, synthesis, and pharmacological evaluation of (S)-4-(5-(1-((1,3,4-thiadiazol-2-yl)amino)-2-methyl-1-oxopropan-2-yl)-5H-chromeno[2,3-b]pyridin-2-yl)-2-fluoro-N,N-dimethylbenzamide (BMS-776532) and its methylene homologue (BMS-791826).

Structurally novel 5H-chromeno[2,3-b]pyridine (azaxanthene) selective glucocorticoid receptor (GR) modulators have been identified. A screening paradigm utilizing cellular assays of GR-mediated transrepression of proinflammatory transcription factors and transactivation of GR-dependent genes combined with three physiologically relevant assays of cytokine induction in human whole blood has allowed for the identification of high affinity, selective GR ligands that display a broad range of pharmacological profiles. Agonist efficacy in reporter assays can be tuned by halogenation of a pendent phenyl ring and correlates well with efficacy for cytokine inhibition in human whole blood. A hypothetical binding mode is proposed, invoking an expanded ligand binding pocket resembling that of arylpyrazole-bound GR structures. Two compounds of close structural similarity (35 and 37; BMS-776532 and BMS-791826, respectively) have been found to maintain distinct and consistent levels of partial agonist efficacy across several assays, displaying anti-inflammatory activity comparable to that of prednisolone 2 in suppressing cytokine production in whole blood and in rodent models of acute and chronic inflammation.